Read this topic

Basic Neurosciences · Paper A

Hormone secretion sites

The idea

Do not memorise which hormone comes from where; learn the one rule that lets you rebuild the table, which is that making a hormone and releasing a hormone are different jobs done by different tissue. The hypothalamus writes instructions. The anterior pituitary reads them and manufactures six hormones of its own. The posterior pituitary manufactures nothing at all — it is the far end of nerve cells whose bodies sit in the hypothalamus, so its two hormones are made upstairs, carried down the stalk and merely stored until a signal releases them. Once that split is fixed, the classic swap becomes impossible to make, the effect of cutting the stalk becomes predictable, and the one hormone that behaves backwards — prolactin, held down rather than driven up — stops being an exception you have to remember and becomes something the rule explains.

How it works

The anatomy dictates the physiology, so start there. Small groups of hypothalamic neurons release hormones into a private set of blood vessels, the hypophyseal portal system, which runs the short distance down the stalk and delivers them at high concentration to the anterior pituitary without ever diluting them in the general circulation. Those releasing hormones tell the anterior pituitary what to make and when: thyrotropin-releasing hormone drives thyroid-stimulating hormone, corticotropin-releasing hormone drives adrenocorticotropic hormone, gonadotropin-releasing hormone drives the two gonadotropins, and growth hormone-releasing hormone drives growth hormone. The anterior pituitary is glandular tissue and its cells synthesise all six of its hormones, four of which act on another endocrine gland further downstream while two act directly on body tissues. The posterior pituitary is built on a completely different plan. It is nervous tissue, not glandular: the cell bodies of its neurons sit in the supraoptic and paraventricular nuclei of the hypothalamus, where antidiuretic hormone and oxytocin are actually synthesised, and their axons run down the stalk to end in the posterior lobe, where the hormones wait in vesicles until an action potential arrives and empties them into the blood. Feedback then closes the system. The hormone produced by the target gland travels back and suppresses both the pituitary and the hypothalamus, which is why measuring a pair of hormones together localises a fault: a low thyroid hormone with a high thyroid-stimulating hormone puts the problem in the thyroid, while a low thyroid hormone with a low or normal stimulating hormone puts it in the pituitary or above. Prolactin is the deliberate exception that proves the design. Its dominant hypothalamic signal is inhibitory — dopamine, flowing continuously down the same portal vessels to hold secretion down — so anything that interrupts that flow, whether a drug that blocks dopamine receptors or physical damage to the stalk, raises prolactin while lowering everything else.

How to spot it

Galactorrhoea in a man taking risperidone is the finding that does not fit an antipsychotic side-effect list until dopamine blockade is remembered.
A serum sodium of one hundred and eighteen in a frail woman on an antidepressant points at inappropriate antidiuretic hormone secretion rather than at anything the pituitary is doing wrong.
Passing four litres of dilute urine on long-term lithium is the finding that rules the pituitary out, because the hormone is present and the kidney is deaf to it.
Loss of body hair and low blood pressure after a road traffic collision points to widespread anterior pituitary failure, and the prolactin in that panel is the one number expected to be high.
Amenorrhoea appearing after an antipsychotic switch is the finding that dates the problem to the prescription rather than to the illness.

Tell it apart

Anterior pituitary vs posterior pituitary — the anterior lobe is glandular tissue that synthesises its own six hormones, while the posterior lobe is nervous tissue that stores and releases two hormones made in the hypothalamus.
Releasing hormone vs tropic hormone — a releasing hormone travels a few centimetres down a private portal circulation to the pituitary, while a tropic hormone travels in the general circulation to a distant gland.
Hypophyseal portal blood vs systemic blood — the portal route delivers hypothalamic hormones undiluted and in high concentration, which is why they act at quantities far too small to work if released into the general circulation.
Antidiuretic hormone and oxytocin vs the anterior six — the first pair are made in the supraoptic and paraventricular nuclei and travel down axons, and the six are made in the pituitary itself.
Prolactin vs every other anterior hormone — prolactin is held down by tonic dopamine inhibition rather than driven up by a releasing hormone, so losing the hypothalamic signal raises it and lowers the rest.
Adrenocorticotropic hormone vs cortisol — the pituitary hormone is the instruction and the adrenal hormone is the product, and which of the two is high tells you whether the fault is above or below the gland.

Watch for

⚠️ Saying the posterior pituitary makes antidiuretic hormone and oxytocin. It stores and releases them; the synthesis happens in hypothalamic cell bodies, and the classic examined swap depends on getting this backwards.
Predicting that stalk damage lowers every pituitary hormone. It lowers the anterior five and raises prolactin, because the interrupted dopamine signal was suppressing it rather than driving it.
Reading a raised prolactin as evidence of a tumour without checking the drug chart. Any antipsychotic that blocks dopamine receptors can raise it, and risperidone, amisulpride and the older typical drugs do so most.
Localising a fault from one hormone alone. A low thyroid hormone means nothing until you see the stimulating hormone beside it, because the pair identifies whether the failure sits in the gland or in the pituitary.
Assuming lithium acts on the pituitary because it causes a form of diabetes insipidus. It makes the collecting ducts of the kidney unresponsive to antidiuretic hormone, so the hormone level is normal or high and desmopressin does not correct it.

Use it again

Ask first whether the hormone in the stem is made where it is released, because that single question resolves most of the anatomy questions in this area.
Trace the chain in the order hypothalamus, pituitary, target gland, and name which link the stem is testing before choosing an answer.
Where a level is abnormal, look for its partner in the pair, since one hormone alone never localises the lesion.
Treat prolactin as running in the opposite direction to everything else whenever a stem involves the stalk, the hypothalamus or a dopamine-blocking drug.
Where a hormone appears to be failing at its target, ask whether the receptor rather than the gland is the problem, as in lithium and the kidney.

In detail

Hook — the question that makes the table unnecessary

A junior colleague is asked in a viva where oxytocin is made. She answers the posterior pituitary, which is the answer almost everyone gives, and it is wrong. Oxytocin is made in the and merely stored in the posterior pituitary until a signal lets it out. That one correction is worth more than any list, because it introduces the only question this topic really asks: is the tissue in front of you making the hormone, or just letting it go? Ask that at every step and you can rebuild the whole endocrine table from first principles rather than trying to hold it in memory.

Plain definition — three structures with three different jobs

The is a small region at the base of the brain that issues chemical instructions. It makes releasing hormones (short-lived signals that travel a few centimetres to tell the pituitary what to produce), and it also makes the two hormones that end up in the posterior pituitary.

The anterior pituitary is a true gland. Its cells manufacture six hormones: thyroid-stimulating hormone, adrenocorticotropic hormone, follicle-stimulating hormone, luteinising hormone, growth hormone and .

The posterior pituitary is not a gland at all. It is the end of a bundle of nerve fibres, and it stores and releases antidiuretic hormone and oxytocin, both made upstairs.

The critical caveat — the swap that costs marks every year

Saying the posterior pituitary makes its two hormones is the classic error, and it survives because the phrase posterior pituitary hormones sounds like a description of origin when it is only a description of exit.

The cell bodies concerned sit in the supraoptic and paraventricular nuclei (two clusters of hypothalamic neurons whose axons run down into the pituitary stalk). Synthesis happens there. The hormone travels down the axon in packets and waits at the far end. When those neurons fire, the packets empty into the bloodstream.

So the posterior lobe follows nervous tissue rules: it has no portal blood supply of its own to speak of, it responds to electrical activity rather than to a releasing hormone, and damage high in the stalk affects it differently from damage to the gland itself.

First principles — the bakery, the locker and the lift

Picture two shops sharing a doorway. Upstairs is a head office writing the day's orders. A short private lift shaft runs down from that office. The bakery's orders ride in it, and the bakery, which has its own ovens, produces six lines: four are dispatched to other shops for finishing, and two are sold straight over the counter.

Next door is a collection locker. It bakes nothing. Everything in it was made in the head office and carried down by hand through the same lift shaft, and it sits there until someone is told to hand it over.

Three predictions fall straight out. Cut the lift and the bakery loses its orders, so its output collapses. Block the shaft high and the locker empties too, because its parcels come down the same shaft: a high stalk lesion takes antidiuretic hormone with it and produces diabetes insipidus, usually permanent because the neurons above die back, whereas a low cut produces at most a transient one, since the hormone can still be released from the stump above the break. And one line in the bakery is unusual: the standing note from the office about it says stop baking rather than bake more, so cutting the lift makes that one line increase. That line is , the note is dopamine, and the prediction is exactly what a severed stalk produces.

Structured walk-through — reading a pair of numbers instead of one

Consider a woman with fatigue and cold intolerance whose free thyroxine comes back low. On its own that number tells you nothing about where the fault lies, so look at the partner. If the thyroid-stimulating hormone is high, the pituitary is shouting at a thyroid that cannot respond, and the problem is in the gland itself.

Now suppose the stimulating hormone comes back low instead, at 0.4 milliunits per litre alongside that low thyroxine. Nothing is shouting. A failing thyroid would have provoked a rise, so the failure must be upstream, in the pituitary or the above it.

Test the reasoning by adding a third number. Her is raised. A pituitary destroyed by infarction would take prolactin down with everything else, but a stalk lesion removes dopamine's brake and pushes it up. So the discordant hormone locates the lesion, and the ordinary sequence — instruction, gland, product, feedback — is what makes that inference available.

Look-alikes & differentials — six sources that get confused

Hormone	Where it is actually made
Thyroid-stimulating hormone, adrenocorticotropic hormone, gonadotropins	Anterior pituitary, synthesised there
Growth hormone,	Anterior pituitary, acting directly on tissue rather than on a gland
Antidiuretic hormone, oxytocin	Hypothalamic nuclei; the posterior lobe only stores and releases
Releasing hormones and dopamine	, delivered by portal veins, never acting at a distance
Cortisol, thyroxine, oestradiol, testosterone	The target glands, and the levels that feed back
Melatonin	Pineal gland, which sits outside this axis entirely

Diagnosis — how a fault in the axis is located

Localisation is done in pairs, never singly: a pituitary hormone measured alongside the product of its target gland. A low product with a high pituitary hormone puts the lesion in the target gland; a low product with a low or inappropriately normal pituitary hormone puts it in the pituitary or .

Dynamic testing extends the same logic where a resting level is ambiguous. The short synacthen test gives synthetic adrenocorticotropic hormone and watches whether the adrenal cortex can respond; a failure to rise indicates the adrenal has lost the , whether primarily or through prolonged lack of stimulation.

Posterior lobe function is assessed by what the kidney does with water. Dilute urine passed in large volumes with a high plasma sodium suggests antidiuretic hormone is missing or ineffective, and the water deprivation test with desmopressin separates the two: a central deficiency concentrates the urine once the hormone is given, whereas a kidney unresponsive to it — the picture produced by long-term lithium — does not. Any raised , meanwhile, is checked against the drug chart before imaging is considered.

Management — the parts a psychiatrist actually handles

Two of these problems are made by psychiatric prescribing, which is why the anatomy is examinable here at all.

Antipsychotic-related (a raised caused by blocking dopamine receptors in the pituitary) is managed by taking a baseline before starting treatment, as NICE CG178 requires, and by acting on symptoms rather than on the number alone. Where amenorrhoea, galactorrhoea or sexual dysfunction appears, the options are dose reduction, a switch to a drug lower on the gradient such as olanzapine or quetiapine, or aripiprazole, which lowers prolactin because it is a at the dopamine receptor. Very high levels, or symptoms in someone whose drug does not raise prolactin, take you back to imaging.

Lithium-related nephrogenic diabetes insipidus (kidney tubules failing to respond to antidiuretic hormone) is managed by monitoring renal function and urine output, reviewing whether lithium remains the right drug, and remembering that desmopressin will not fix it. Replacement in hypopituitarism follows a fixed order that is worth knowing: hydrocortisone before thyroxine, because raising the metabolic rate first can precipitate an adrenal crisis.

Exam pearl — made here, or only released here

The single question that unlocks the topic is whether the structure named manufactures the hormone or only lets it out. Six hormones are made in the anterior pituitary; two are made in hypothalamic nuclei and stored in the posterior lobe; and one anterior hormone, , is governed by a brake rather than an accelerator. Test yourself now: a patient has a raised prolactin and low levels of everything else the pituitary makes. Can you say where the lesion is, and name the two commonest explanations for a raised prolactin in a psychiatric clinic before you reach for a scan?

In one line — the route, not the list

Carry the route rather than the table: instructions from the , a private lift to a gland that makes six of its own, a storage depot next door that makes none, feedback from the target gland closing the loop, and one hormone held down rather than driven up.