HUMB1001 — Module 1 — Control of Body Systems

HUMB1001 · Integrated Systems Anatomy and Physiology

Module 1
Control of Body Systems

How the nervous and endocrine systems keep the body working as one

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In this lecture

Two control systems
Conscious or automatic?
The brain's automatic centres
Where the systems meet
How hormones talk to cells
Keeping hormones in range
A tour of the endocrine glands

FRAG 0: Welcome to Integrated Systems Anatomy and Physiology, or ISAP for short. In Human Structure and Function, you met the body one system at a time. This unit builds on that. Over the semester we'll look at how the body's systems work together. We'll start with how the body is controlled, then work through support and movement, the heart and circulation, the kidneys, the lungs and gas transport, digestion, and finally reproduction. Throughout, one idea ties everything together: homeostasis. The body constantly senses change and corrects for it, and much of this unit is about how it does that. You'll also be learning alongside students from many different courses, and that's deliberate. Whatever you go on to do, whether that's nursing, pharmacy, a therapy, laboratory science or another health profession, you'll work in teams where everyone shares the same basic understanding of how the body works. This unit is where that shared understanding starts. So talk to the people around you in labs and tutorials. They'll bring a different perspective to the same body. Each week follows the same rhythm. This online lecture introduces the ideas. Then you'll apply them in the science laboratory, often in the Anatomy Facility with real specimens, and in your tutorial. This lecture isn't a video. It's an interactive lecture, and it works a little differently. The narration you're hearing is an AI-generated voice reading a script written by your teaching team. Everything moves at your pace. Use the controls at the bottom of the screen to pause, or to speed the narration up to one and a half or two times. Some slides will stop and wait for you: a question to answer, something to sort, a diagram to explore. Those aren't marked, so take your time and have a genuine go before checking your answer. That's where most of the learning happens. At the end there's a short reflection, and it becomes a page of notes you can print or save. In this first module, we'll look at the two systems that control everything else: the nervous system and the endocrine system. Let's begin.

Acknowledgement of Country (Boodja). I would like to acknowledge the Whadjuk Noongar people whose land we are standing on and recognise the strength, resilience and capacity of the Noongar people where Curtin University is situated. I pay my respect to their vibrant and endless culture and the leadership of the Elders past, present and future. This country (boodja) where Curtin University is situated has belonged to the Whadjuk Noongar people for thousands of years and is a place of learning for all people now and Curtin University is very proud to continue on this very long tradition.

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What you'll be able to do

Two control systems

Nervous vs endocrine: speed, reach, duration

Conscious or automatic?

Pathways to the cortex, and the reflex arc

Mapping the brain

Cerebral lobes · brainstem · diencephalon

Where the systems meet

Hypothalamus → pituitary, two routes

How hormones work

Chemistry decides transport and action

Keeping hormones in range

Feedback loops and the major glands

FRAG 0: Here's where we're headed. This is a big module because it underpins everything that follows. When we get to the heart, the kidneys or the gut, you'll find the same nerves and hormones doing the controlling. By the end of this lecture, you should be able to do six things. FRAG 1: First, compare the body's two control systems, the nervous system and the endocrine system. You should be able to explain how each one sends its message, how quickly it works and how long its effects last. Then explain why the body needs both of them rather than just one. FRAG 2: Second, trace the route a signal takes when you consciously feel something and decide to act on it, from a receptor in your skin all the way up to your cerebral cortex and back down to a muscle. Then compare that with a reflex, and explain the difference between somatic and autonomic reflexes. FRAG 3: Third, find your way around the brain. That means naming the lobes of the cerebrum and what each one does, the three parts of the brainstem and the vital centres they contain, and the diencephalon. We'll spend the most time on its most important structure, the hypothalamus. FRAG 4: Fourth, explain how the hypothalamus controls the pituitary gland. This is where the nervous and endocrine systems join. You'll see that the front and back of this small gland develop from different tissues, and so the hypothalamus controls them in two completely different ways. FRAG 5: Fifth, explain how a hormone's chemistry, whether it dissolves in water or in lipid, determines three things: how it travels in the blood, where its receptor sits on the target cell, and how it changes what that cell does. FRAG 6: And finally, describe how hormone release is switched on and off, mostly by negative feedback and occasionally by positive feedback. Then locate the major endocrine glands in the body and link each gland's structure to the hormones it makes.

Two ways to send a message

One system uses wires. The other broadcasts.

Only cells with the right receptor are listening.

FRAG 0: Every organ in your body needs instructions: when to contract, when to secrete, when to speed up or slow down. There are really only two ways to deliver those instructions. The first is the nervous system, which works like a network of private phone lines. A neuron runs directly to a particular muscle or gland. When it fires, the message arrives within milliseconds, at exactly one address, and nobody else hears it. FRAG 1: The second is the endocrine system, which works more like a radio broadcast. A gland releases a hormone into the blood, and the blood carries it to almost every cell in the body. But a broadcast is only useful to someone with a receiver tuned to the right station. In the same way, only cells that carry a receptor for that particular hormone respond. Every other cell ignores it completely. Hold on to that idea, because it keeps coming back. Receptors decide which cells respond to a hormone.

Nervous vs endocrine

FeatureNervousEndocrine

Messenger

Action potentials + neurotransmitters

Hormones

Route

Along neurons, to one target

In the blood, body-wide

Speed

Milliseconds

Seconds or longer

Duration

Brief

Minutes to years

Who responds

Cells the neuron contacts

Any cell with the receptor

FRAG 0: Let's put the two systems side by side and compare them on five features. As we go, notice that each system's strengths are the other system's weaknesses. That's exactly why the body needs both. FRAG 1: The nervous system sends its signal in two stages. First, an action potential travels as an electrical signal along a neuron. Then, at the synapse, the neuron releases a neurotransmitter that crosses a tiny gap to the next cell. The endocrine system relies on one type of messenger, hormones. These are chemicals made by specialised secretory cells, either scattered through tissues or grouped together into glands. FRAG 2: A nerve signal follows a fixed path, along an axon to one particular muscle, gland or neuron. A hormone has no path of its own. It's released into the interstitial fluid around the gland, diffuses into nearby capillaries, and from there the bloodstream carries it around the entire body. FRAG 3: That difference in route makes a big difference to speed. A nervous response can happen within milliseconds, which is fast enough to catch yourself when you trip. A hormone has to be secreted, travel through the circulation, reach its target and then change what that cell does. So hormonal responses take seconds at the very least, and often much longer. FRAG 4: The trade-off is how long the effect lasts. Once a neuron stops firing, its neurotransmitter is cleared from the synapse and the effect stops almost straight away. Hormonal effects can last minutes or days, or even years. Think of how long you kept growing through childhood and adolescence. That was growth hormone, working over more than a decade. FRAG 5: Finally, which cells respond. A neuron only affects the cells it synapses with. A hormone reaches everything, but only affects cells with the right receptor. So a hormone's effect can be very local if its receptors are only on one tissue, or it can spread right across the body if almost every cell has them. You'll see both kinds of hormone in this module.

Which pair matches each response to the system that mainly controls it?Response 1: your pupils constrict in bright sunlight · Response 2: you grow taller over the years of puberty

How confident are you?

Pupil constriction is a reflex. It's fast, brief and aimed at one target, the smooth muscle of the iris, so it's a job for neurons. Growing taller takes years and needs tissues all over the body to respond, especially bone and muscle, so it's a job for a hormone (growth hormone).

Compare the two responses using the table you've just seen. Your pupils adjust in a fraction of a second and only one small muscle is involved, which points to the nervous system. Growth takes years and involves almost every tissue, which points to a hormone (growth hormone).

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Section 2

Conscious or automatic?

How the nervous system controls the body

The nervous system has two parts

BrainSpinal cordCranial nervesSpinal nerves

FRAG 0: Anatomically, the nervous system has two divisions. The central nervous system, or CNS, is the brain and spinal cord. It's where information is received, compared with what's already there, and acted on, and where decisions are made. The peripheral nervous system, or PNS, is everything outside it: the nerves that carry information into the CNS from the body, and carry commands back out again. FRAG 1: First, the brain, which sits protected inside the skull. It contains around eighty-six billion neurons, and it's the only place where conscious awareness happens. Anything you're aware of feeling, seeing or deciding is happening here. FRAG 2: Continuous with the brain is the spinal cord. It leaves the skull through the large opening at its base, the foramen magnum, and runs down inside the vertebral canal. In adults, it ends at about the level of the first or second lumbar vertebra, well above the bottom of the spine. The spinal cord isn't just a cable. As you'll see shortly, it can make decisions of its own. FRAG 3: Now the peripheral nervous system. Twelve pairs of cranial nerves connect directly to the brain. They mostly serve the head and neck: the eyes, ears, nose, tongue and the muscles of the face. One important exception, the vagus nerve, wanders all the way down into the chest and abdomen. FRAG 4: And thirty-one pairs of spinal nerves connect to the spinal cord, one pair at each level, exiting between the vertebrae. Between them, they supply the rest of the body: the trunk, the limbs and many of the internal organs. So any signal travelling between your big toe and your brain uses a spinal nerve for part of the journey and the spinal cord for the rest.

Four major regions

CerebrumDiencephalonBrainstemCerebellum

FRAG 0: Here's the brain cut straight down the middle, from front to back. This is called a midsagittal section, and you'll see this view a lot, both in this lecture and in the lab. It shows the four major regions of the brain. FRAG 1: The largest region by far is the cerebrum, which makes up about eighty percent of the brain's mass. It's divided into left and right cerebral hemispheres, and its outer layer, the cerebral cortex, is where conscious thought, sensation, voluntary movement, language and memory are processed. FRAG 2: Tucked underneath the cerebrum, right in the centre of the brain, is the diencephalon. You can only see it properly in a section like this one. It's small, but it contains two structures we'll keep returning to: the thalamus, a relay station for sensory information, and the hypothalamus, which is the body's main homeostatic control centre. FRAG 3: Below the diencephalon is the brainstem. It's the oldest part of the brain in evolutionary terms, and it connects the rest of the brain to the spinal cord. It's small but vital. Its centres keep your heart beating and your lungs breathing without you ever having to think about it. FRAG 4: And at the back, tucked under the cerebrum, is the cerebellum, meaning "little brain". It doesn't start movements. It compares the movement you intended with the movement that's actually happening, and fine-tunes it, which keeps you coordinated and balanced. We'll come back to it in the module on movement.

Lobes of the cerebrum

Frontal

Voluntary movement · planning · personality

Parietal

Body sensation: touch, pain, temperature

Temporal

Hearing · smell · memory

Occipital

Vision

Insula

Taste · sensations from the viscera

FRAG 0: Let's look at the cerebrum from the side. Its surface is folded into ridges called gyri, separated by grooves called sulci. A few of the grooves are deep and consistent enough to act as landmarks. The central sulcus runs across the top of the brain from side to side. The lateral sulcus runs along the side. A deep cleft, the longitudinal fissure, separates the two hemispheres. These landmarks divide each hemisphere into five lobes, and most are named after the skull bone that covers them. FRAG 1: At the front, and in front of the central sulcus, is the frontal lobe. The gyrus just in front of the central sulcus is the primary motor cortex. It's where voluntary movement begins, and we'll trace a movement from here in a moment. The rest of the frontal lobe deals with planning, decision-making, motivation, mood and much of what we'd call personality. It also contains an area that controls the muscles you use to speak. FRAG 2: Behind the central sulcus is the parietal lobe. The gyrus just behind that sulcus is the primary somatosensory cortex. It's where you consciously feel touch, pressure, pain and temperature from all over your body. It's organised like a map: each part of this gyrus receives sensation from a specific part of the body. So the central sulcus separates movement in front of it from sensation behind it. FRAG 3: Below the lateral sulcus is the temporal lobe. It contains the primary auditory cortex, where sound is consciously heard, and it's also involved in the sense of smell. Deeper inside the temporal lobe are structures that are essential for forming new memories. FRAG 4: At the very back is the occipital lobe. It's devoted almost entirely to vision. Information from your eyes travels all the way to the back of the brain before you consciously see anything. That's why a hard knock to the back of the head can make you "see stars". FRAG 5: Finally, the insula. It's hidden deep inside the lateral sulcus, covered by the frontal, parietal and temporal lobes, so you have to pull them apart to see it. The insula is involved in taste and in your awareness of what's happening inside your own body, such as the sensations from your viscera. Remember these lobes when you get to the lab, because you'll be finding them on real specimens.

The cerebral cortex

A thin sheet, heavily folded.

Folding = more grey matter in the same skull.

FRAG 0: If you cut the cerebrum across, the way you'll see it in the lab, you'll notice that its outer layer is darker than the tissue underneath. That outer layer is the cerebral cortex. It's grey matter, made mostly of neuron cell bodies and synapses, and it's surprisingly thin: only about two to four millimetres deep. Underneath it is white matter, made of myelinated axons that carry signals between different parts of the cortex and down to the rest of the nervous system. FRAG 1: So why is the cortex folded? The folds follow the gyri and sulci, and they let a very large sheet of grey matter fit inside a skull of limited size. Roughly two-thirds of the cortex is hidden inside the sulci, out of sight. More cortex means more neurons and more synapses, and that's what makes complex conscious processing possible: recognising a face, understanding a sentence, planning your next move. So whenever we say something is "conscious", we mean it involves the cerebral cortex.

Feeling something: the conscious sensory route

Receptor

Detects the stimulus

Sensory neuron

Into the spinal cord

Ascending tract

Up the spinal cord, through the brainstem

Thalamus

Relay and filter

Cerebral cortex

Conscious awareness

FRAG 0: Let's follow a signal the whole way. Imagine you touch something with your fingertip, perhaps the edge of a desk or a cup of coffee, and you become aware of it. For that awareness to happen, the signal has to travel all the way to your cerebral cortex. Here's the route it takes. FRAG 1: It starts at a receptor, a specialised structure in your skin that responds to a particular kind of stimulus, such as pressure, temperature or stretch. When the stimulus is strong enough, the receptor produces action potentials. That's how the information is converted into the nervous system's own language. FRAG 2: Those action potentials travel along a sensory neuron, which is also called an afferent neuron, meaning it carries signals towards the CNS. It runs from your fingertip, through a spinal nerve, and enters the spinal cord. It hasn't reached the brain yet, but the signal is now inside the central nervous system. FRAG 3: In the spinal cord, the signal is carried upwards in bundles of axons called ascending tracts. They're called ascending because they run up towards the brain. The signal travels up the length of the cord and then through the brainstem. Along the way, most sensory pathways cross to the opposite side of the body. That's why the left side of your brain feels the right side of your body. FRAG 4: Next, the signal reaches the thalamus, in the diencephalon. The thalamus is a relay station. Almost every sensation you're aware of passes through it on the way to the cortex. The thalamus also filters, deciding which signals are important enough to pass on. It's the reason you don't notice the feel of your clothes all day. FRAG 5: Finally, the thalamus relays the signal to the cerebral cortex, to the primary somatosensory cortex in the parietal lobe, the gyrus you met a moment ago. Only now are you consciously aware that you've touched something, where on your body it was, and what it felt like. Count the handovers: that's several neurons and several synapses before you feel anything.

Deciding to move: the conscious motor route

Motor cortex

The decision to move

Descending tract

Through the brainstem, down the cord

Synapse

Onto a motor neuron

Motor neuron

Out through a spinal nerve

Effector

Skeletal muscle contracts

FRAG 0: Now the return journey. You've felt the cup, and you decide to pick it up. A voluntary, conscious movement like this runs the pathway in the opposite direction, from the cortex down to a muscle. FRAG 1: It begins in the primary motor cortex, the gyrus in front of the central sulcus in the frontal lobe. This is where the decision to move becomes a command. Neurons here fire in the particular pattern needed for that movement. For a skilled task, like playing the piano or riding a bike, many other areas of the brain help to plan and coordinate that pattern first. FRAG 2: The command travels down through the white matter of the cerebrum and the brainstem, in bundles of axons called descending tracts. Most of these fibres cross to the opposite side in the medulla, so your left motor cortex controls the right side of your body. The tract then continues down the spinal cord to the level that serves the muscle you want to move. FRAG 3: At that level, the descending axon synapses in the spinal cord with a motor neuron, which is also called an efferent neuron, meaning it carries signals away from the CNS. This is another handover and another synapse. FRAG 4: The motor neuron's axon leaves the spinal cord, travels through a spinal nerve, and runs all the way out to the muscle. In your arm, that axon can be well over half a metre long. That's one single cell stretching from your spinal cord to your forearm. FRAG 5: Finally, it reaches the effector, the structure that carries out the response. For conscious movement, the effector is always skeletal muscle. The motor neuron releases its neurotransmitter, the muscle fibres contract, and your hand closes around the cup. The whole process, from the decision in your cortex to the contraction in your arm, took a fraction of a second. But as you'll see, a fraction of a second isn't always fast enough.

Conscious control has a cost

Every synapse adds a delay.

Sometimes the body can't wait for a decision.

FRAG 0: Conscious control is powerful. It lets you do enormously complicated things, like writing, playing sport or painting, that need input from many areas of the brain at once. But that complexity has a price. The signal has to travel a long way, up to the cortex and back down again, and it has to cross many synapses along the way. Each synapse adds a small delay while the neurotransmitter is released, crosses the gap and acts on the next cell. Add enough synapses together, and the decision takes time. FRAG 1: Most of the time, that doesn't matter. But imagine your hand is on a hot stovetop. If you had to wait for the sensation to reach your cortex, for you to realise it was hot, decide to move and send the command back down, you'd be burned before your hand moved. So for situations like this, the body has a shortcut. It skips the conscious brain entirely. That shortcut is the reflex.

What makes a reflex a reflex?

Involuntary

No decision involved

Rapid

Few synapses

Predictable

Same stimulus, same response

Unlearnt

Built in, not practised

FRAG 0: A reflex is an automatic response to a stimulus that happens without conscious thought. Every reflex shares four features, and together they explain why reflexes are so useful for protecting the body and keeping it stable. FRAG 1: First, reflexes are involuntary. You don't decide to do them, and often you can't stop them either. Think of blinking when something flies towards your eye. By the time you're aware of what happened, the reflex has already happened. Your awareness comes afterwards, if at all. FRAG 2: Second, they're rapid. That's because a reflex pathway is short and has very few synapses. Remember that each synapse adds a delay. The simplest reflexes have only one synapse between the sensory neuron and the motor neuron. That's how a reflex can respond faster than any conscious decision. FRAG 3: Third, they're predictable. The same stimulus produces the same response every time. That's what makes reflexes so useful clinically. When a doctor taps your knee with a reflex hammer, they know exactly what should happen. If it doesn't happen, or it's exaggerated, that tells them something about the pathway involved. FRAG 4: And fourth, they're unlearnt. You were born with these pathways already wired in. Practice doesn't create a reflex, and it doesn't improve one. That's different from a skill like touch typing, which feels automatic after enough practice but still relies on learned patterns in your brain. Each reflex uses its own specific neural pathway, called a reflex arc.

The reflex arc

Receptor

Detects the stimulus

Sensory neuron

Carries it into the CNS

Integration centre

Spinal cord or brainstem

Motor neuron

Carries the command out

Effector

Muscle or gland responds

FRAG 0: Every reflex arc, from the knee-jerk to the control of your heart rate, is built from the same five components. Let's work through them using the example of pulling your hand away from a hot stovetop. This is called the withdrawal reflex. FRAG 1: It starts with a receptor. Here, it's a pain receptor in the skin of your hand that responds to the heat and damage. Just like in the conscious pathway, the receptor turns the stimulus into action potentials. FRAG 2: The action potentials travel along a sensory neuron into the spinal cord. So far, this is exactly the same as the conscious route. The difference is what happens next. FRAG 3: Instead of sending the signal straight up to the brain, the spinal cord deals with it on the spot. This is the integration centre: the part of the CNS where the incoming signal is processed and a response is chosen. In the withdrawal reflex, the sensory neuron synapses with a small interneuron in the grey matter of the spinal cord, and that interneuron passes the signal to a motor neuron. For some reflexes the integration centre is in the brainstem instead of the spinal cord. And in the very simplest reflexes, like the knee-jerk, there's no interneuron at all. The sensory neuron synapses directly on the motor neuron. That's called a monosynaptic reflex. FRAG 4: The motor neuron then carries the command out of the spinal cord, through a spinal nerve, and towards the arm. FRAG 5: And finally, the effector: the muscle or gland that carries out the response. Here, it's the flexor muscles of your arm, which contract and pull your hand away. All of this happens within the spinal cord. The signal does still travel up to your brain as well, which is why you feel the pain and say "ouch". But by the time you feel it, your hand has already moved.

You step on a drawing pin and lift your foot. Put the reflex arc in order.

Drag the steps into order, first at the top, or use the arrow buttons.

⋮⋮Leg flexor muscles contract
⋮⋮Pain receptor in the sole of the foot
⋮⋮Motor neuron to the leg
⋮⋮Sensory neuron to the spinal cord
⋮⋮Interneuron in the spinal cord grey matter

Correct. That's the arc: receptor → sensory neuron → integration centre → motor neuron → effector. The spinal cord handles this one without the brain.

Not quite. Follow the signal: it has to be detected first, carried into the CNS, processed there, carried back out, and only then can anything happen.

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Somatic vs autonomic reflexes

FeatureSomaticAutonomic (visceral)

Effector

Skeletal muscle

Smooth muscle, cardiac muscle, glands

Purpose

Protection, balance and posture

Keeping internal conditions stable

Integration centre

Spinal cord or brain

Spinal cord or brainstem

Examples

Knee-jerk, withdrawal

Heart rate, blood pressure, pupil size, bladder emptying

FRAG 0: Reflexes come in two functional types. What decides which type a reflex is? Not how fast it is, and not where it's integrated. It's the kind of effector the reflex acts on. Let's compare the two. FRAG 1: Somatic reflexes act on skeletal muscle, the same muscle you move voluntarily. The withdrawal reflex and the knee-jerk are both somatic, because the response is a skeletal muscle contracting. Autonomic reflexes, also called visceral reflexes, act on everything else: smooth muscle, like the walls of blood vessels, the airways and the gut; cardiac muscle in the heart; and glands, like the salivary glands. FRAG 2: That difference in effector leads to a difference in purpose. Somatic reflexes mostly protect you. They pull you away from painful stimuli and keep you balanced and upright. Autonomic reflexes do the constant, invisible work of homeostasis. They adjust heart rate, blood pressure, breathing, digestion and the emptying of the bladder and bowel, usually without you noticing at all. FRAG 3: Both types use the same five-part arc, and both can be integrated in the spinal cord or the brain. The knee-jerk is integrated in the spinal cord, but somatic reflexes of the head, like blinking, are integrated in the brainstem. Among autonomic reflexes, emptying the bladder and bowel are integrated low in the spinal cord, in its sacral region. Heart rate, blood pressure and breathing are integrated in the brainstem and act through the autonomic nervous system. We'll meet those brainstem centres in the next section. FRAG 4: So, examples. Somatic: the knee-jerk, the withdrawal reflex, and the constant small adjustments that keep you upright when a bus brakes suddenly. Autonomic: your heart rate slowing when your blood pressure rises, and your bladder contracting when it's full. As a toddler you learned to override that reflex consciously, so there's a limit to how involuntary it is. And one you've already met in this lecture: your pupils constricting in bright light. That's an autonomic reflex, because the effector is smooth muscle in the iris.

Drag each reflex into the correct category.

Drag each item, or click it and then click where it goes

Heart rate slows when blood pressure rises

Knee-jerk when the patellar tendon is tapped

Pupils constrict in bright light

Staying upright when the bus brakes

Pulling your hand off a hot pan

Salivating at the smell of food

Bladder contracts when full

Somatic

Autonomic

All correct. Skeletal muscle means somatic; smooth muscle, cardiac muscle or a gland means autonomic.

Not quite yet. The ones outlined in red are in the wrong place. Ask yourself which effector responds. Is it skeletal muscle, or smooth muscle, cardiac muscle or a gland?

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Section 3

The brain's automatic centres

Brainstem and diencephalon

The brainstem

Medulla oblongata

Heart rate · blood vessel diameter · breathing rhythm · cough, sneeze, swallow, vomit

Pons

The “bridge” · REM sleep · helps set breathing

Midbrain

Visual and auditory reflexes · pupil reflex · steadying movement

FRAG 0: The brainstem is the stalk that connects the rest of the brain to the spinal cord, and it has three parts. In evolutionary terms it's the oldest part of the brain, and it looks after the most basic functions of all. Two things are true of every part of it. First, it's full of white matter: ascending and descending tracts, which means every signal travelling between the brain and the spinal cord has to pass through here. Second, scattered among those tracts are clusters of grey matter called nuclei. Many of them are integration centres for vital reflexes. So even small damage in the brainstem can be life-threatening. That's why, after a serious head injury, clinicians test brainstem reflexes, like the pupils' response to light, to check how the brainstem is working. FRAG 1: The lowest part is the medulla oblongata, which is continuous with the spinal cord below. It's where the descending motor tracts cross to the other side, as you saw a moment ago. Its nuclei are the integration centres for some of the most essential autonomic reflexes. The cardiac centre adjusts heart rate. The vasomotor centre adjusts the diameter of blood vessels, and so helps control blood pressure. The medullary rhythmicity centre sets the basic rhythm of breathing. The medulla also coordinates a set of protective reflexes: coughing, sneezing, swallowing, vomiting and even hiccupping. You'll meet the cardiac, vasomotor and respiratory centres again in later modules, so remember they're here. FRAG 2: Above the medulla is the pons, the rounded bulge on the front of the brainstem. "Pons" is Latin for "bridge", and it's a good name. Its white matter tracts connect the medulla, the midbrain and the cerebellum, and carry signals up and down between the spinal cord and the brain. It contains a sleep centre that helps start REM sleep, the stage of sleep when most dreaming happens. It also contains the pontine respiratory centre, which works together with the medullary rhythmicity centre. The medulla sets the basic rhythm of breathing, and the pons helps smooth the switch between breathing in and breathing out. FRAG 3: The top part of the brainstem is the midbrain, between the pons and the diencephalon. Again, it's full of ascending and descending tracts. It also has nuclei that help stabilise and coordinate movement. One of them, the substantia nigra, is the area that degenerates in Parkinson's disease. The midbrain is also the integration centre for important visual and auditory reflexes. The visual reflexes coordinate your head and eye movements, so you can track a moving object without losing it. The auditory reflexes include the startle reflex, when you jump and turn towards a sudden loud noise. And do you remember your pupils shrinking in bright light, from the first question in this lecture? That autonomic reflex is integrated here, in the midbrain.

The diencephalon

Thalamus

Sensory relay and filter

Epithalamus

Pineal gland · melatonin · daily rhythms

Hypothalamus

Homeostatic control centre

FRAG 0: Sitting on top of the brainstem, in the very centre of the brain, is the diencephalon. The cerebrum almost completely surrounds it, which is why you can only really see it in a section like this one. It has several parts. The smallest, the subthalamus, lies off to the side where this midline view can't show it, and it helps to control movement. We'll focus on the other three. FRAG 1: The largest part is the thalamus. It's actually a pair of egg-shaped masses, one in each hemisphere, joined across the midline. You've already met it in this lecture. It's the relay station that almost every sensation you're aware of passes through on its way to the cerebral cortex. Remember that it also filters, deciding what's important enough to pass on. That's why you can sleep through familiar noises but wake straight away to your own name. FRAG 2: Behind and above the thalamus is the epithalamus. Its most important part is the pineal gland, a small, pine-cone-shaped structure. The pineal gland is an endocrine gland inside the brain. It secretes the hormone melatonin, mostly at night and in the dark. Melatonin helps set the body's daily, or circadian, rhythms, including when you feel sleepy. The epithalamus is also involved in emotional responses. This is our first example of the nervous and endocrine systems overlapping: a hormone-secreting gland that is part of the brain itself. FRAG 3: Below the thalamus, forming the floor of the diencephalon, is the hypothalamus. For its size, it's the most important structure in this lecture. It's only about as big as an almond, less than one percent of the brain's mass, and yet it's the body's main control centre for homeostasis. Notice the stalk hanging down from its base, called the infundibulum, with the pituitary gland on the end. That connection is where the nervous system takes control of the endocrine system, and it's where we're heading next. First, though, let's look at what the hypothalamus actually does.

The hypothalamus runs homeostasis

Body temperature

Heat loss vs heat gain

Sleep–wake cycles

The body's master clock

Food intake

Hunger and fullness

Water balance

Thirst and water retention

Autonomic control

Heart, smooth muscle, glands

Pituitary control

Directs the endocrine system

FRAG 0: The hypothalamus is shaped roughly like an upside-down triangle. Its point faces forwards and down, towards the pituitary gland. It's joined to the pituitary in two ways. Anatomically, it's connected by the infundibulum, the stalk you just saw. Functionally, it's connected by blood vessels and by bundles of nerve fibres. The hypothalamus works like a thermostat for many different variables at once. It monitors the state of the body, compares it with where it should be, and triggers a correction. Here are six of the things it controls. FRAG 1: First, body temperature. The hypothalamus receives information about the temperature of the blood and the skin. When you're too hot, it triggers sweating and widens the blood vessels in your skin to lose heat. When you're too cold, it narrows those vessels and triggers shivering to generate heat. A fever is the hypothalamus deliberately turning its set point up. FRAG 2: Second, sleep–wake cycles. A small cluster of neurons in the hypothalamus acts as the body's master clock. It receives information directly from the eyes about light and dark, and uses it to keep your daily rhythms in time with the day. That's partly how it tells the pineal gland when to release melatonin. Jet lag is what happens when this clock and the local time don't match. FRAG 3: Third, food intake. Centres in the hypothalamus respond to nutrient levels in the blood and to hormones from the gut and fat tissue. They produce the feelings of hunger that make you eat, and of fullness that make you stop. FRAG 4: Fourth, water balance and thirst. Specialised cells in the hypothalamus detect when the blood becomes too concentrated, for example after a salty meal or when you're dehydrated. The hypothalamus responds in two ways: it makes you feel thirsty, and it triggers the release of a hormone that tells the kidneys to hold on to water. You'll meet that hormone in the next section. FRAG 5: Fifth, autonomic control. The hypothalamus sits above the brainstem centres you've just seen, and adjusts them. Through the autonomic nervous system, it influences heart rate, blood pressure, the smooth muscle of the gut and the secretion of glands. That's how an emotion, like fear, can make your heart pound and your mouth go dry. FRAG 6: And sixth, control of the pituitary gland. The hypothalamus decides when the pituitary releases its hormones, and through them it controls many of the other endocrine glands in the body. So the hypothalamus is where the nervous system takes charge of the endocrine system. That's so important that it gets its own section, which starts after this quick check.

A patient has damage that affects their heart rate, blood pressure and breathing rhythm. Click the region most likely to be involved.

Click a numbered marker.

Correct: the medulla oblongata. It contains the cardiac centre, the vasomotor centre and the medullary rhythmicity centre, which is why damage here is so often life-threatening.

Not quite. The pons helps with breathing, and the hypothalamus adjusts heart rate and blood pressure from above, but the centres that directly control all three are lower down in the brainstem. Look for the part continuous with the spinal cord.

Section 4

Where the systems meet

The hypothalamus and the pituitary gland

One gland, two origins

1 · Two buds

FRAG 0: The pituitary gland is about the size of a pea, roughly one centimetre across. It sits in a small hollow in the bone at the base of the skull, directly below the hypothalamus, attached by a stalk called the infundibulum. It's sometimes called the hypophysis. To understand how the hypothalamus controls it, you first need to know something unusual about how it forms. The pituitary isn't one gland. It's two, made from two completely different tissues. Early in development, two small buds start to grow towards each other. From above, a bud grows down from the floor of the developing brain. From below, a pouch grows up from the roof of the developing mouth. FRAG 1: The two buds keep growing until they meet. The pouch from the mouth, called Rathke's pouch, ends up in front, pressed against the stalk that has grown down from the brain. At this stage the pouch is still open to the mouth below. The two tissues are touching, but they're still completely separate tissues with different origins, and they'll stay that way. FRAG 2: Next, the pouch loses its connection to the mouth and separates completely. What's left of the connection disappears, so in the adult there's no link at all between the pituitary and the mouth. The pouch wraps around the front of the neural stalk, and from here on the two parts develop together, side by side, inside a single capsule. From the outside it looks like one gland. Inside, it's still two. FRAG 3: Here's the result in the adult. At the back is the posterior pituitary, also called the neurohypophysis. It grew down from the brain, so it's still made of neural tissue, and it's still physically connected to the hypothalamus through the infundibulum. In front is the anterior pituitary, also called the adenohypophysis. "Adeno" means gland. It came from the roof of the mouth, so it's made of glandular, hormone-secreting cells, and it has no nerve connection to the brain at all. So the same small gland holds two tissues with two different origins. That's the key to the whole section. Because the two lobes are built differently, the hypothalamus has to talk to each of them in a different way.

Two routes from the hypothalamus

Releasing & inhibiting hormones

Made by hypothalamic neurons

Portal system

A private blood route down the stalk

Anterior pituitary responds

Releases its own hormones

Neurosecretory cells

Hormone made in the hypothalamus

The tract

Carried down axons in the stalk

Posterior pituitary releases

Stored, then released on a nerve signal

FRAG 0: This is the most important diagram in this section, so take your time with it. On the left is the route the hypothalamus uses to control the anterior pituitary. On the right is the route to the posterior pituitary. One route uses blood vessels, and the other uses nerve fibres. That matches exactly what you've just seen: the anterior lobe has no nerve connection to the brain, and the posterior lobe is made of neural tissue. FRAG 1: Start on the left. Neurons in the hypothalamus make small hormones of their own, called releasing hormones and inhibiting hormones. A releasing hormone tells the anterior pituitary to release more of a particular hormone, and an inhibiting hormone tells it to release less. These neurons secrete them into a network of capillaries at the top of the stalk. FRAG 2: From those capillaries, the blood flows down the stalk in small veins and straight into a second network of capillaries in the anterior pituitary. Two capillary networks linked by veins like this are called a portal system. This one is the hypothalamohypophysial portal system. Normally, anything secreted into the blood is diluted through the whole circulation. The portal system delivers the hypothalamus's hormones directly to the anterior pituitary in high concentration, so only tiny amounts are needed. FRAG 3: The glandular cells of the anterior pituitary respond. Depending on which releasing or inhibiting hormone reached them, they increase or decrease the secretion of their own hormones. Those hormones enter the capillaries and leave the pituitary in the general circulation, to act on targets all over the body. So the anterior pituitary makes its own hormones, but the hypothalamus decides when they're released. FRAG 4: Now the right side, which works quite differently. Here, the hormones are made in the hypothalamus itself, in the cell bodies of two groups of specialised neurons called neurosecretory cells. These neurons are nerve cells that release hormones instead of neurotransmitters. FRAG 5: The hormones are packaged and carried down the neurons' long axons, through the middle of the stalk. This bundle of axons is called the hypothalamohypophysial tract. Notice the difference in names: portal system on the left, because it's blood vessels, and tract on the right, because it's nerve fibres. FRAG 6: The hormones are stored in the axon terminals in the posterior pituitary. When the neurosecretory cells fire action potentials, the terminals release them into the capillaries, and they enter the blood. So the posterior pituitary doesn't make any hormones of its own. It stores and releases hormones made by the hypothalamus. It's really an extension of the brain.

Anterior vs posterior pituitary

FeatureAnterior (adenohypophysis)Posterior (neurohypophysis)

Tissue

Glandular, from roof of mouth

Neural, from brain

Size

70–80% of gland

20–30% of gland

Link to hypothalamus

Blood: portal system

Nerves: tract

Hormones made

In the anterior pituitary

In the hypothalamus

Number of hormones

Seven

Two

FRAG 0: Let's gather that together and compare the two lobes directly. If you can reproduce this table from memory, you understand the hypothalamus–pituitary connection. FRAG 1: The anterior pituitary is glandular tissue, because it developed from the roof of the mouth. Its cells are specialised to make and secrete hormones. The posterior pituitary is neural tissue, because it grew down from the brain. It's made mostly of axons and their supporting cells. Every other difference in this table follows from this one, so if you forget the rest, start here and work it out. FRAG 2: The anterior lobe is by far the larger of the two, making up about seventy to eighty percent of the gland. The posterior lobe makes up the remaining twenty to thirty percent. You'll see this clearly under the microscope in the lab. The two lobes look completely different, because they're completely different tissues. FRAG 3: Because the anterior pituitary has no nerve connection to the hypothalamus, the hypothalamus has to reach it through the blood, using releasing and inhibiting hormones carried in the portal system. The posterior pituitary is connected directly, by the axons of the hypothalamohypophysial tract, which run all the way down into it. So if you're asked how the hypothalamus controls each lobe, the short answer is: blood for the anterior lobe, nerves for the posterior. FRAG 4: This is the difference students most often get wrong, so it's worth slowing down. The anterior pituitary makes its own hormones in its own glandular cells. The hypothalamus only controls when they're released. The posterior pituitary makes nothing. Its two hormones are made in the cell bodies of neurons in the hypothalamus, and the posterior lobe simply stores them and releases them into the blood when those neurons fire. FRAG 5: And finally, the numbers. The anterior pituitary secretes seven hormones, and they affect almost every part of the body, including several other endocrine glands. The posterior pituitary releases just two, but both are important. Let's meet all nine, starting with the anterior seven.

Seven anterior pituitary hormones ★ = tropic

Growth hormone (GH)

Most body tissues

Thyroid-stimulating hormone (TSH) ★

Thyroid gland

Adrenocorticotropic hormone (ACTH) ★

Adrenal cortex

Follicle-stimulating hormone (FSH) ★

Ovaries and testes

Luteinising hormone (LH) ★

Ovaries and testes

Prolactin

Mammary glands

Melanocyte-stimulating hormone (MSH)

Skin melanocytes

FRAG 0: Here are the seven hormones of the anterior pituitary, each with its main target. Before we start, one new term. Four of these hormones are marked with a star. They're called tropic hormones. A tropic hormone is a hormone whose target is another endocrine gland: it tells that gland to release its own hormones. So the hypothalamus controls the anterior pituitary, and the anterior pituitary, through its tropic hormones, controls several other glands. It's a chain of command, and it's why the pituitary is sometimes called the master gland. FRAG 1: Growth hormone acts on most tissues in the body. It stimulates growth, especially of bone and muscle, by increasing protein synthesis and cell division. It also shifts the body towards using fat for energy. Much of its effect on growth happens indirectly, through growth factors that it stimulates the liver to release. It's the hormone that kept you growing through childhood. FRAG 2: Thyroid-stimulating hormone is the first of the tropic hormones. Its target is the thyroid gland, which it stimulates to release thyroid hormones. Those hormones in turn raise the metabolic rate of cells all over the body. We'll use this chain as our main example of feedback later in the lecture. FRAG 3: Adrenocorticotropic hormone, usually shortened to ACTH, is also tropic. Its target is the adrenal cortex, the outer layer of the adrenal glands above the kidneys. Note that it's the cortex only, not the inner medulla. ACTH stimulates the cortex to release cortisol, an important hormone in the response to stress. FRAG 4: Follicle-stimulating hormone, FSH, targets the gonads, the ovaries and testes. In the ovaries, it stimulates the development of follicles, each containing an egg. In the testes, it supports sperm production. FRAG 5: Luteinising hormone, LH, also targets the ovaries and testes. In the ovaries, a surge of LH triggers ovulation. In the testes, it stimulates the production of testosterone. FSH and LH are called gonadotropins, and we'll come back to them in the reproduction modules at the end of the unit. FRAG 6: Prolactin mainly targets the mammary glands, where it stimulates milk production after childbirth. It isn't a tropic hormone, because its main target isn't another endocrine gland. FRAG 7: And finally, melanocyte-stimulating hormone, MSH, which acts on melanocytes, the pigment-producing cells of the skin. In humans, its role in normal skin colour is relatively small. So that's seven hormones, and four of them are tropic.

Two posterior pituitary hormones

Antidiuretic hormone (ADH)

Kidneys hold on to water

Oxytocin

Uterus and mammary glands

FRAG 0: Now the posterior pituitary, and its two hormones. Remember that neither of them is made here. Both are made by the neurosecretory cells of the hypothalamus, carried down the tract, and stored in the posterior lobe until they're needed. Each is made by its own group of cell bodies in the hypothalamus. FRAG 1: The first is antidiuretic hormone, or ADH. "Diuresis" means producing a lot of urine, so an antidiuretic hormone reduces urine output. It acts on the kidneys, making them hold on to water and return it to the blood rather than losing it in the urine. This is the hormone we mentioned earlier, when the hypothalamus detects that the blood has become too concentrated. It releases ADH, and more water is kept in the body. At high levels, ADH also constricts blood vessels, which is why it's also called vasopressin. You'll see much more of it in the kidney module. FRAG 2: The second is oxytocin. It acts on smooth muscle in two places. In the uterus, it causes the strong contractions of labour. In the mammary glands, it causes milk to be squeezed out, or ejected, during breastfeeding. Keep oxytocin in mind: at the end of the lecture it will be our example of a rare type of control called positive feedback.

Drag each hormone to its main target.

Drag each item, or click it and then click where it goes

Prolactin

ADH

MSH

ACTH

Oxytocin

FSH

TSH

Most body tissues

Thyroid gland

Adrenal cortex

Ovaries and testes (×2)

Mammary glands (milk production)

Skin melanocytes

Kidneys

Uterus (contractions)

All correct. ADH and oxytocin come from the posterior pituitary; the rest come from the anterior pituitary.

Not quite yet. The ones outlined in red are in the wrong place. Many of these names tell you the target. Look inside the name: “thyroid-stimulating”, “adrenocorticotropic”, “antidiuretic”.

Press → to continue

Section 5

How hormones talk to cells

Chemistry decides everything

How far does the signal travel?

Autocrine – the same cell

FRAG 0: Hormones aren't the only chemical signals in the body. Cells release chemical messengers all the time, and we classify these signals by one simple feature: how far the message travels before it reaches the cell that responds. The endocrine system is one of four types of chemical signalling, and it's easiest to understand next to the others. The first, and shortest, is autocrine signalling. "Auto" means self. An autocrine chemical is released by a cell and acts on that same cell. For example, some white blood cells release chemicals that stimulate their own activity and multiplication during an immune response, amplifying it. FRAG 1: A little further is paracrine signalling. "Para" means beside. A paracrine chemical is released into the tissue fluid and diffuses a short distance to act on neighbouring cells, without entering the blood. A classic example is histamine. When tissue is injured, white blood cells nearby release histamine, which causes the local swelling, redness and itch you'll recognise from an insect bite. The effect stays local. FRAG 2: And then there's endocrine signalling, the subject of this lecture. An endocrine chemical, a hormone, is released into the tissue fluid, enters the capillaries and is carried in the blood to target cells that can be a long way from the gland that made it. Notice what decides who responds. The hormone passes almost every cell in the body, but only cells with the right receptor respond. The grey cells in the diagram don't have receptors, so they don't respond at all. FRAG 3: For completeness, here's how the nervous system does it. A neuron releases a neurotransmitter into a synapse, a gap so narrow that the signal reaches just one cell almost instantly. It's still a chemical signal, but it's the most targeted of all. Putting all four side by side shows the two control systems in one picture: the endocrine system broadcasts a signal widely, and the nervous system delivers it privately.

Endocrine vs exocrine glands

FeatureEndocrineExocrine

Ducts

None: ductless

Yes

Secretes into

Tissue fluid → blood

A surface or cavity, via the duct

Product

Hormones

Sweat, saliva, tears, mucus, enzymes

Examples

Pituitary, thyroid, ovaries, testes

Sweat, salivary, lacrimal, mucous glands

FRAG 0: The word "gland" gets used for two very different kinds of structure, and it's important to keep them apart. Both are made of cells that secrete something. The difference is where the secretion goes. FRAG 1: Endocrine glands are ductless. They have no tube to carry their secretion anywhere. Exocrine glands do have ducts, and each duct leads to a specific place. "Endo" means within, and "exo" means outside. That's a useful clue: endocrine glands secrete inside the body, into the blood; exocrine glands secrete out onto a surface. FRAG 2: So an endocrine gland releases its hormone into the interstitial fluid around its cells. From there, the hormone diffuses into nearby capillaries and is carried throughout the body. That's why endocrine glands have a very rich blood supply. An exocrine gland releases its secretion into its duct, which delivers it to a specific place: the surface of the skin, the inside of the mouth, the surface of the eye, or the inside of the gut. FRAG 3: The products are different too. Endocrine glands secrete hormones. Exocrine secretions aren't hormones. They're things like sweat, saliva, tears, mucus and digestive enzymes, which do their job at the place where they're delivered. FRAG 4: Some examples. The pituitary, the thyroid, the ovaries and the testes are endocrine glands. Sweat glands, salivary glands, the lacrimal glands that make tears, and the mucous glands lining the airways and gut are exocrine. And one organ is both. The pancreas has exocrine tissue that makes digestive enzymes and releases them down a duct into the small intestine, and it also has small islands of endocrine cells that release insulin and glucagon into the blood. We'll come back to that at the end of the lecture.

Solubility decides everything

FeatureWater-solubleLipid-soluble

Chemical class

Proteins, peptides, most amino-acid derivatives

Steroids (from cholesterol) + thyroid hormones

Examples

All pituitary hormones, insulin, glucagon, adrenaline

Cortisol, aldosterone, testosterone, oestrogen, T3/T4

In the blood

Dissolved, free in plasma

Bound to a carrier protein

How long it lasts

Minutes; broken down quickly

Longer; protected by its carrier

Receptor

On the cell membrane

Inside the cell

Mechanism

Indirect (second messenger)

Direct (acts on genes)

FRAG 0: This is the central idea of this section, and one of the most useful ideas in the whole lecture. Chemically, hormones fall into two broad groups. Which group a hormone belongs to decides almost everything about it: how it travels in the blood, how long it lasts, where its receptor is and how it changes the target cell. And it all comes down to one property: whether the hormone dissolves in water or in lipid. Let's build the table one row at a time. FRAG 1: Most hormones are made from amino acids. That includes proteins, which are long chains of amino acids; peptides, which are short chains; and some hormones made from a single modified amino acid, such as adrenaline. These are water-soluble. The other group is the steroid hormones, which are made from cholesterol, and they're lipid-soluble. There's one important exception. The thyroid hormones, T3 and T4, are made from an amino acid, but they behave like lipid-soluble hormones. They're a favourite exam question, so remember them. FRAG 2: Some examples of each. Every hormone from the pituitary gland is water-soluble. So are insulin and glucagon from the pancreas, ADH, parathyroid hormone and adrenaline. On the lipid-soluble side are the steroids: cortisol and aldosterone from the adrenal cortex, and the sex hormones testosterone, oestrogen and progesterone. And, as the exception, T3 and T4. FRAG 3: Now think about how each type travels in the blood. Plasma is mostly water. A water-soluble hormone simply dissolves in it and travels free. A lipid-soluble hormone doesn't dissolve well in plasma, so it binds to a carrier protein, a special binding protein that holds it in the blood. The binding is reversible. When the hormone reaches the tissues, it lets go of the carrier and becomes free to act. FRAG 4: That affects how long a hormone lasts. Free water-soluble hormones are broken down and cleared quickly, often within minutes, so their effects stop quickly unless more hormone is secreted. Bound lipid-soluble hormones are protected by their carrier, so they last much longer in the blood, from hours to days. The bound hormone acts as a reserve that's released gradually. FRAG 5: Now the receptor. Remember that a hormone only affects cells with its receptor. But where is that receptor? The cell membrane is made of lipid. A lipid-soluble hormone can diffuse straight through it, so its receptor is inside the cell, in the cytoplasm or the nucleus. A water-soluble hormone can't cross the lipid membrane, so it has to be recognised from outside. Its receptor sits on the outer surface of the cell membrane. FRAG 6: And that decides the mechanism. A lipid-soluble hormone gets inside and acts directly, by switching specific genes on or off. We call this the direct mechanism. A water-soluble hormone never enters the cell. It binds to the outside, and the cell passes the message inside using a second messenger. We call this the indirect mechanism. Let's look at each one, starting with the direct mechanism.

The direct mechanism

1Diffuses through the membrane

2Binds its receptor inside the cell

3Hormone–receptor complex binds DNA

4Gene switched on → mRNA

5New proteins change the cell

FRAG 0: Here's a target cell, and a steroid hormone arriving in the blood, still bound to its carrier protein. Watch what happens as it acts on the cell. This is the direct mechanism, and it works the same way for all the lipid-soluble hormones: the steroids and the thyroid hormones. FRAG 1: In the tissue, the hormone lets go of its carrier, leaves the capillary and reaches the target cell. Because it's lipid-soluble, the cell membrane isn't a barrier. The hormone simply diffuses through the lipid bilayer and into the cytoplasm. No door, no special transporter: it goes straight through. FRAG 2: Inside, it meets its receptor. Depending on the hormone, the receptor may be waiting in the cytoplasm, or already inside the nucleus. Only cells that make this receptor can respond. Every other cell lets the hormone pass through without any effect. FRAG 3: The hormone and receptor together form a hormone–receptor complex. The complex moves into the nucleus, through the nuclear envelope, and binds to specific regions of DNA. That's what makes this mechanism "direct": the hormone ends up acting on the cell's genes itself. FRAG 4: Binding to the DNA switches particular genes on, or sometimes off. When a gene is switched on, it's copied into messenger RNA. The mRNA leaves the nucleus and travels to the ribosomes in the cytoplasm. FRAG 5: At the ribosomes, the mRNA is used to build new proteins. Those proteins are what actually change the cell. They might be enzymes that speed up a reaction, transporters that change what the membrane lets through, or structural proteins that change how the cell's organelles work. Notice the consequence. Making new proteins takes time, so the direct mechanism is slow to start, usually hours. But once the new proteins are there, the effect lasts, often for hours or days. That's the pattern you'd expect of lipid-soluble hormones like cortisol and the sex hormones.

The indirect (second-messenger) mechanism

1Hormone binds a surface receptor

2G protein activated

3Adenylate cyclase switched on

4ATP → cAMP (second messenger)

5Protein kinases → cell responses

6cAMP broken down → effect stops

FRAG 0: Now the other type: a water-soluble hormone, such as TSH, ADH or glucagon. It can't get through the cell membrane, so it has to deliver its message from outside, and the cell has to relay that message inside. The relay uses a chain of molecules called a second-messenger system. The most common one uses a molecule called cyclic AMP, and it's the one we'll follow. FRAG 1: The hormone arrives and binds to its receptor on the outer surface of the cell membrane. The hormone itself goes no further. It stays outside the cell the whole time. Because it's the hormone that carries the message to the cell, we call it the first messenger. FRAG 2: Binding changes the shape of the receptor, and that change is felt on the inside of the membrane. There, the receptor activates a G protein, a protein complex attached to the inner surface of the membrane. The G protein is the go-between. It passes the signal from the receptor to the next molecule in the chain. FRAG 3: The activated G protein switches on an enzyme in the membrane called adenylate cyclase. Some G proteins inhibit this enzyme instead, which lets some hormones turn a cell's activity down rather than up. We'll follow the stimulating version. FRAG 4: Adenylate cyclase converts ATP, the cell's energy molecule, into cyclic AMP, or cAMP. This is the second messenger: it carries the message the rest of the way, through the cytoplasm. Notice something important. One hormone molecule leads to the production of many cAMP molecules, and that's called amplification. It's why tiny amounts of hormone in the blood can have large effects on a cell. FRAG 5: cAMP activates enzymes called protein kinases, which switch other proteins on or off. That's how the cell's behaviour actually changes. Depending on the cell, the result might be a change in membrane permeability, the activation of other enzymes, increased protein synthesis, the secretion of a product, or the contraction or relaxation of muscle. All of this uses proteins already in the cell, so it's fast: within seconds to minutes. FRAG 6: Finally, the switch-off. cAMP is broken down quickly by another enzyme, and once it's gone, the kinases stop and the effect ends. So to keep the response going, more hormone has to keep arriving. Compare this with the direct mechanism: the indirect mechanism is fast to start and quick to stop, and the direct mechanism is slow to start and long-lasting. Both patterns follow from the hormone's chemistry, just as the table said they would.

Sort each hormone by where its receptor is.

Drag each item, or click it and then click where it goes

Adrenaline

TSH

Testosterone

Glucagon

Parathyroid hormone

Insulin

Aldosterone

Cortisol

ADH

T3 / T4 (thyroid hormones)

Oestrogen

Receptor inside the cell (direct)

Receptor on the membrane (indirect)

All correct. Did T3/T4 and adrenaline catch you out? Both are made from a single amino acid, but T3/T4 behave like lipid-soluble hormones and adrenaline doesn't.

Not quite yet. The ones outlined in red are in the wrong place. First ask: is it a steroid, a thyroid hormone, or made from amino acids? Then ask: can it cross a lipid membrane?

Press → to continue

Section 6

Keeping hormones in range

What switches hormone release on and off?

Three triggers for hormone release

Humoral

The gland senses the blood directly · e.g. low Ca²⁺ → PTH

Neural

Nerves stimulate the gland · e.g. sympathetic → adrenaline

Hormonal

Another hormone stimulates it · e.g. TSH → T3/T4

FRAG 0: Most hormone levels are kept within a narrow, healthy range. When the level falls too low, the gland has to secrete more. When it rises too high, secretion has to be suppressed. But what actually tells a gland to secrete? There are three kinds of trigger, and every endocrine gland responds to at least one of them. FRAG 1: The first is a humoral stimulus. "Humoral" is an old word for the body fluids, and here it means the blood. The gland's own cells monitor the level of something in the blood and respond to it directly, with no nerve or other hormone in between. For example, the cells of the parathyroid glands constantly monitor the level of calcium ions in the blood. When calcium falls, they secrete parathyroid hormone, or PTH, which acts to bring calcium back up. The cells of the pancreas that secrete insulin work the same way, responding directly to blood glucose. FRAG 2: The second is a neural stimulus, where nerves stimulate the gland directly. This is the least common of the three. The classic example is the adrenal medulla, the inner part of the adrenal gland. When you're frightened or stressed, neurons of the sympathetic nervous system stimulate the adrenal medulla, and the neurotransmitter they release makes its cells secrete adrenaline and noradrenaline into the blood. This is another place where the nervous and endocrine systems meet, and it gives you the rush of fight or flight within seconds. FRAG 3: The third is a hormonal stimulus, where one hormone triggers the release of another. You've already met this idea: it's what tropic hormones do. For example, thyroid-stimulating hormone from the anterior pituitary stimulates the thyroid gland to secrete its hormones, T3 and T4. And the pituitary itself is triggered hormonally, by releasing hormones from the hypothalamus. Chains of hormonal stimuli like this are called axes, and we'll look at one in detail in a moment.

Two kinds of feedback

Negative feedback reverses a change. Positive feedback amplifies it.

Positive feedback needs an end point.

FRAG 0: Once a hormone is released, something has to stop the release going on forever. In most cases, that something is the hormone's own effect. This is called feedback. By far the most common type is negative feedback. In negative feedback, the response pushes the variable in the opposite direction to the original change. If a variable rises, the response brings it back down. If it falls, the response brings it back up. It's exactly how a thermostat works. When the room gets too warm, the heater switches off, and when it gets too cool, the heater switches back on. Negative feedback is stabilising, and it's the basis of homeostasis. Almost every hormone in the body is controlled this way. FRAG 1: Positive feedback is much less common, and it works the other way. The response pushes the variable further in the same direction as the original change. A rise causes a bigger rise, which causes a bigger rise again. That isn't stabilising at all: it's a runaway. So positive feedback is only useful when the body needs something to build up quickly to a climax and then finish. That means every positive feedback loop needs something outside the loop to stop it. We'll see an example at the end of this section. First, two examples of negative feedback: one simple, and one with several steps.

A direct loop: glucose and insulin

1Blood glucose rises

2Pancreatic beta cells detect it

3Insulin released

4Cells take up glucose

5Glucose falls → insulin release falls

FRAG 0: Here's negative feedback at its simplest: the control of blood glucose by the hormone insulin. The variable being controlled is the concentration of glucose in the blood, shown by the gauge in the middle. The shaded band is the normal range, and the loop's job is to keep the gauge inside it. FRAG 1: Imagine you've just eaten a meal rich in carbohydrate, like a bowl of pasta. As it's digested, the starch is broken down into glucose, which is absorbed from the small intestine into the blood. Within half an hour or so, your blood glucose level rises above the normal range. That's the change, or stimulus, that the loop has to correct. FRAG 2: The rise is detected by beta cells in the pancreas. They sit in small clusters of endocrine cells called pancreatic islets, scattered through the pancreas. Beta cells sense the glucose level in the blood flowing past them directly. This is the humoral stimulus you just met: no nerves and no other hormones are involved. The beta cells act as both the sensor and the control centre of this loop. FRAG 3: In response, the beta cells secrete insulin into the blood. The more the glucose rises, the more insulin they release, so the size of the response is matched to the size of the problem. Insulin is a protein, so it's water-soluble. It travels free in the plasma and acts on receptors on the surface of its target cells. FRAG 4: Insulin travels in the blood to cells all over the body, especially in the liver, skeletal muscle and fat. There it binds its receptors on the cell membranes and causes the cells to take up glucose from the blood, and to store it. As glucose moves out of the blood and into the cells, the blood glucose level falls back towards normal. FRAG 5: And here's the feedback. As the glucose level falls, the stimulus to the beta cells gets weaker, so they secrete less insulin. The response has removed its own stimulus. A rise in glucose led to a response that lowered glucose, the opposite direction to the change, and that's what makes it negative feedback. The pancreas also has a second hormone, glucagon, that works the other way when glucose falls too low. We'll meet it at the end of the lecture.

An indirect loop: the thyroid axis

Hypothalamus → TRH

Releasing hormone, via the portal system

Anterior pituitary → TSH

A tropic hormone

Thyroid → T3 and T4

Into the blood

Body cells

Metabolic rate rises

Negative feedback

T3/T4 inhibit the hypothalamus and pituitary

FRAG 0: The glucose loop had one gland and one hormone. Many hormones are controlled by a longer chain, with the hypothalamus at the top, the anterior pituitary in the middle and a target gland at the bottom. Chains like this are called axes. Let's follow one of the most important, the hypothalamic–pituitary–thyroid axis. It brings together almost everything in this lecture. FRAG 1: It starts in the hypothalamus. Neurons there secrete thyrotropin-releasing hormone, or TRH. As its name says, it's a releasing hormone. TRH enters the capillaries of the portal system and travels the short distance down the stalk to the anterior pituitary, just as you saw in Section 4. FRAG 2: TRH stimulates cells in the anterior pituitary to secrete thyroid-stimulating hormone, TSH, into the general circulation. TSH is one of the tropic hormones: its target is another endocrine gland. FRAG 3: TSH travels in the blood to the thyroid gland in the neck, and stimulates it to make and release its two hormones, T3 and T4. Remember that these are the exception in the hormone chemistry table: made from an amino acid, but lipid-soluble. FRAG 4: T3 and T4 act on cells all over the body. Being lipid-soluble, they enter the cells and act directly on genes. They raise the metabolic rate, so cells use more oxygen and produce more heat, and they increase protein synthesis. That's why someone whose thyroid is underactive often feels cold and tired, and someone whose thyroid is overactive often feels hot and restless. FRAG 5: Now the feedback. T3 and T4 in the blood also act back on the top of the chain. They inhibit the anterior pituitary, reducing TSH secretion, and they inhibit the hypothalamus, reducing TRH secretion. So when T3 and T4 levels rise, the signals driving their own production are turned down, and the levels fall back. When T3 and T4 fall, that inhibition eases, TRH and TSH rise, and the thyroid is stimulated again. It's still negative feedback. The loop is just longer: the final product switches off the steps that produce it.

Break the axis

TRH

TSH

T3 / T4

Metabolic rate

Shaded band = normal range

1 · Choose a scenario

2 · Predict: what will happen to TSH?

Compare scenarios 2 and 5. In both, T3/T4 is low. How could a blood test tell them apart?

Positive feedback in action

Labour has begun. The baby's head presses down on the cervix, stretching it. Each contraction pushes the baby further down, and the cervix stretches further.

The rule

Stretch → oxytocin → contraction → more stretch. The loop only stops when the baby is born and the stretch is removed.

FRAG 0: Now the rarer type, positive feedback. The best-known example involves a hormone you met in Section 4: oxytocin, from the posterior pituitary. Labour has begun. The baby's head is pressing down on the cervix, the narrow opening at the base of the uterus, and stretching it. Stretch receptors in the cervix send nerve signals up to the hypothalamus. The hypothalamus responds by stimulating the release of oxytocin from the posterior pituitary. Remember, it's made in the hypothalamus and stored in the posterior lobe. Oxytocin travels in the blood to the uterus, and makes its smooth muscle contract more strongly. Those stronger contractions push the baby further down against the cervix, and stretch it even more. FRAG 1: And that's the loop. More stretch causes more oxytocin, which causes stronger contractions, which cause more stretch. The response doesn't oppose the stimulus: it reinforces it, so contractions build in strength and frequency. That's exactly what's needed to deliver a baby. But as you'd expect of positive feedback, the loop can't stop itself. What ends it comes from outside the loop: the baby is born, the stretch on the cervix is removed, and oxytocin release falls. The same pattern appears in milk ejection during breastfeeding, where the baby's suckling triggers oxytocin release, and in blood clotting, where each step of the process speeds up the next until the clot has formed. In each case there's a clear end point. Positive feedback drives a process to completion. Negative feedback holds things steady.

A patient has taken a high daily dose of prednisolone, a drug that acts like cortisol, for three months. What has most likely happened to the ACTH secreted by their anterior pituitary?

How confident are you?

The hypothalamus and pituitary can't tell the drug from the body's own cortisol. High “cortisol” levels switch off the signals from the top of the axis by negative feedback, so ACTH falls, and without ACTH the adrenal cortex becomes less active. That's why a drug like this must be reduced gradually rather than stopped suddenly: the patient's own adrenal glands need time to start working again.

Think about the thyroid axis you just explored, especially the “too many thyroid tablets” scenario. The cortisol axis works the same way: hypothalamus → pituitary (ACTH) → adrenal cortex (cortisol), with cortisol feeding back negatively on the top of the axis. A drug that acts like cortisol does the same.

Press → to continue

Section 7

A tour of the endocrine glands

Where they are, and how their structure fits their job

The endocrine map

Click any numbered gland

Choose a gland

Main hormones

–

Where you'll meet it

–

Gold = dedicated endocrine glands · green = organs that also contain endocrine cells

The thyroid and parathyroid glands

Thyroid gland

Two lobes + isthmus, in front of the trachea

Follicles

Store hormone as thyroglobulin → T3/T4

Parafollicular cells

Calcitonin: lowers blood Ca²⁺

Parathyroid glands

PTH: raises blood Ca²⁺

FRAG 0: We'll start in the neck, with the thyroid and the parathyroid glands. They sit together, but they're structurally and functionally separate glands, and between them they give us a lovely example of structure fitting function. They also show how two hormones can control one variable from opposite directions. FRAG 1: The thyroid gland lies in the front of the neck, just below the larynx, wrapped around the front of the trachea. It's shaped like a butterfly, with a right lobe and a left lobe joined across the midline by a narrow band of tissue called the isthmus. It has one of the richest blood supplies of any organ in the body for its size, which suits a gland whose whole job is to release hormones into the blood. FRAG 2: Under the microscope, the thyroid is made of thousands of small hollow spheres called follicles. Each follicle is lined by a single layer of cuboidal follicular cells. The centre is filled with a protein-rich material called thyroglobulin, which contains the thyroid hormones in an inactive, stored form. This structure is unusual. Most endocrine glands store only small amounts of hormone, but the thyroid keeps a large reserve outside its cells, in the follicles. When TSH arrives, the follicular cells take up some of the stored thyroglobulin, release the active hormones T3 and T4, and secrete them into the capillaries between the follicles. T3 is also called triiodothyronine, and T4 thyroxine. FRAG 3: Between the follicles is a second, completely different group of endocrine cells: the parafollicular cells. They secrete a hormone called calcitonin, which lowers the level of calcium in the blood. It does this mainly by promoting the deposit of calcium into bone, and by increasing the loss of calcium in the urine. FRAG 4: On the back of the thyroid are the parathyroid glands, usually four small pea-shaped glands, two on each lobe. They secrete parathyroid hormone, PTH, which you met as our example of a humoral stimulus. PTH does the opposite of calcitonin: it raises blood calcium. It releases calcium from bone, reduces the calcium lost in the urine, and activates vitamin D, which increases calcium absorption from the gut. So blood calcium is controlled by a pair of hormones working in opposite directions, one lowering it and one raising it. That keeps it tightly within its normal range, which matters because nerves and muscles, including the heart, depend on it. You'll see the same kind of opposing pair again shortly.

The adrenal glands

Adrenal glands

On top of each kidney · cortex + medulla

Zona glomerulosa

Aldosterone: kidneys retain Na⁺

Zona fasciculata

Cortisol: ↑ blood glucose, stress response

Zona reticularis

Androgens

Medulla

Adrenaline + noradrenaline · sympathetic control

FRAG 0: Next, the adrenal glands, also called the suprarenal glands. Like the pituitary, each one is really two glands in one, with two different origins, two kinds of tissue and two kinds of hormone. If you've understood the pituitary, you'll recognise the pattern. FRAG 1: There's one adrenal gland on top of each kidney, and each is shaped like a flattened pyramid wrapped in a thin capsule. In section, you can see two distinct regions. The outer region is the adrenal cortex, which is glandular tissue. The inner region is the adrenal medulla, which is related to nervous tissue. Every hormone of the cortex is a steroid, and every hormone of the medulla is made from an amino acid. Using Section 5, you can already predict how each type travels in the blood and acts on its target cells. FRAG 2: The cortex has three layers, or zones, each making a different class of steroid hormone. The outermost is the zona glomerulosa. It makes mineralocorticoids, which regulate the body's minerals, or electrolytes. The main one is aldosterone, which makes the kidneys retain sodium, and water follows the sodium. Aldosterone is controlled mainly by blood potassium levels and by a hormone system triggered by the kidneys, which you'll meet in the kidney module. FRAG 3: The middle zone, the thickest, is the zona fasciculata. It makes glucocorticoids, mainly cortisol. Cortisol helps the body cope with longer-term stress. Among other things, it raises blood glucose so that energy is available, and it suppresses inflammation. Its release is controlled by ACTH from the anterior pituitary. That's the axis from the prednisolone question a few slides ago. FRAG 4: The innermost zone of the cortex is the zona reticularis, which makes androgens. These are steroid sex hormones. After puberty, the much larger amounts made by the ovaries and testes usually overshadow them, but adrenal androgens still contribute to things like body hair. FRAG 5: And in the centre is the adrenal medulla. Its cells are closely related to sympathetic neurons. In fact, they're essentially modified neurons that release their chemical into the blood instead of into a synapse. When the sympathetic nervous system is activated, in fright, fight or flight, nerves stimulate the medulla directly. That's the neural stimulus from S38. The medulla then releases adrenaline and noradrenaline, also called epinephrine and norepinephrine. They're made from an amino acid, so they're water-soluble, act on membrane receptors and work within seconds, raising heart rate, blood pressure and blood glucose for immediate action. So the adrenal gland contains both kinds of stress response. The medulla handles the fast, short-term response, and the cortex, through cortisol, handles the slower, longer-lasting one.

The pancreas

Head, body, tail · behind the stomach

Exocrine acini (≈ 99%)

Enzymes → duct → duodenum

Pancreatic islets (≈ 1%)

Endocrine · into the blood

Beta cells

Insulin: lowers blood glucose

Alpha cells

Glucagon: raises blood glucose

FRAG 0: Our last gland is the pancreas, which we've mentioned several times already. It's the clearest example in the body of one organ doing two very different jobs, and its microscopic structure shows you exactly how. FRAG 1: The pancreas lies in the abdomen, behind the stomach. It's about twelve to fifteen centimetres long and has three regions. The head sits in the C-shaped curve of the duodenum, the first part of the small intestine. The body runs across the back of the abdomen, and the tail reaches towards the spleen. Students often mistake the spleen for the kidney in the lab, so look carefully. FRAG 2: About ninety-nine percent of the pancreas is exocrine tissue. It's made of clusters of cells called acini, which secrete digestive enzymes. The enzymes drain through a system of ducts into the main pancreatic duct, which empties into the duodenum. This is exactly the exocrine pattern from Section 5: a duct, delivering a non-hormone product to a specific place. FRAG 3: Scattered among the acini, like small islands, are the pancreatic islets, sometimes called the islets of Langerhans. They make up only about one percent of the pancreas, and they're the endocrine part. They have no ducts. Instead, each islet is threaded with capillaries, and its cells secrete their hormones straight into the blood. Under the microscope, the islets look noticeably paler than the dark acini around them, which makes them easy to spot. The islets contain several cell types, and we'll focus on the two main ones. FRAG 4: The majority of islet cells are beta cells, which secrete insulin. You've already followed insulin's negative feedback loop. It's released when blood glucose rises, for example after a meal, and it makes cells in the liver, muscle and fat take up glucose and amino acids, which lowers blood glucose. FRAG 5: The alpha cells secrete glucagon, which does the opposite. When blood glucose falls, for example between meals or during fasting, glucagon is released. It acts mainly on the liver, making it break down its stored glycogen and release glucose into the blood, which raises blood glucose. So here's another opposing pair of hormones, just like calcitonin and PTH for calcium. Insulin lowers glucose and glucagon raises it, and between them they hold blood glucose within its normal range. A third, smaller group of islet cells, the delta cells, secretes somatostatin, which helps to regulate the other two. Both insulin and glucagon are peptides, so they're water-soluble and act on membrane receptors.

Which gland releases hormones into the blood in direct response to signals from sympathetic neurons? Click it.

Click a numbered marker.

Correct: the adrenal glands, specifically the adrenal medulla. Its cells are modified sympathetic neurons, so sympathetic nerves stimulate them directly (a neural stimulus), and they release adrenaline and noradrenaline within seconds.

Not quite. You're looking for the classic neural stimulus, where nerves trigger the gland directly. Think about which gland's inner region is made of modified sympathetic neurons.

Five big ideas

Two systems, one goal

Fast and private vs slow and broadcast

Reflexes skip the decision

Speed through fewer synapses

The hypothalamus is the bridge

Blood to the anterior, nerves to the posterior

Solubility decides

Transport, receptor and mechanism

Negative feedback holds the line

Positive feedback finishes the job

FRAG 0: We've covered a lot of ground. Before you reflect on it, here are the five big ideas to take away. If you understand these, the details will hang together, and you'll find them again in every module that follows. FRAG 1: First: the body has two control systems with the same goal, homeostasis, but very different methods. The nervous system is fast, precise and brief: a private line to one target. The endocrine system is slower, widespread and long-lasting: a broadcast that only cells with the right receptor hear. The body needs both, and they constantly work together. FRAG 2: Second: conscious control runs through the cerebral cortex, which is powerful but slow, because of all the synapses along the way. Reflexes skip the conscious decision. With a five-part arc and very few synapses, they respond quickly and predictably. Somatic reflexes act on skeletal muscle, and autonomic reflexes act on smooth muscle, cardiac muscle and glands. FRAG 3: Third: the hypothalamus is where the two systems meet. It controls the anterior pituitary through the blood, with releasing and inhibiting hormones carried in the portal system. It controls the posterior pituitary through nerves, with hormones it makes itself, carried down the tract. And through the pituitary's tropic hormones, it controls many other glands. FRAG 4: Fourth: a hormone's chemistry decides how it works. Water-soluble hormones travel free, bind receptors on the membrane and act quickly through second messengers. Lipid-soluble hormones travel on carrier proteins, enter the cell, act directly on genes, and act more slowly but for longer. The thyroid hormones are the exception to remember. FRAG 5: And fifth: hormone levels are controlled mainly by negative feedback, where the response reverses the change and holds a variable steady. That's true whether the loop is short, like glucose and insulin, or long, like the thyroid axis. Positive feedback is rare, and it's used to drive a process to completion, like childbirth.

Reflect

1. Explain to a friend who isn't studying health why the body needs both a nervous and an endocrine system. Use one example of each.

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2. Choose one idea from this lecture that you think will matter in your future profession, and explain why.

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HUMB1001 · Module 1 · Control of Body Systems — my notes

Five big ideas

Two systems, one goal — Fast and private vs slow and broadcast
Reflexes skip the decision — Speed through fewer synapses
The hypothalamus is the bridge — Blood to the anterior, nerves to the posterior
Solubility decides — Transport, receptor and mechanism
Negative feedback holds the line — Positive feedback finishes the job

My reflections

Explain to a friend who isn't studying health why the body needs both a nervous and an endocrine system. Use one example of each.

Choose one idea from this lecture that you think will matter in your future profession, and explain why.

Before your lab this week

Read the textbook sections on the thyroid, parathyroid, adrenal glands and pancreas
Complete the pre-lab activity and print your lab notes
Bring a clean lab coat, safety glasses and closed-in shoes
Try the Module 1 revision quizzes and FeedForward questions

FRAG 0: Here's your notes page. It brings together the five big ideas and your own reflections, and you can print it or save it as a PDF. Before your lab this week, there are a few things to do. Read the textbook sections on the thyroid, the parathyroid glands, the adrenal glands and the pancreas. The four glands we've just toured are exactly what you'll examine in the lab. Complete the pre-lab activity, and print your lab notes to bring with you. Don't forget your lab coat, safety glasses and closed-in shoes, because you can't enter the laboratory without them. After the lab, the revision quizzes and the FeedForward questions on the unit site are a good way to check your understanding. They're not marked, so use them as often as you like. That's the end of Module 1. You now know how the body controls itself, and every module from here on builds on it. Next week, we'll look at how the body is supported. See you in the lab.