The hypothalamic–pituitary axis

How the hypothalamus and pituitary run the thyroid, adrenal, gonadal, growth and milk axes through feedback, and the drugs that act at each level.

Updated Nov 2, 2026

The hypothalamus sends releasing and inhibiting hormones down a small portal blood system to the anterior pituitary, which then drives peripheral glands. The posterior pituitary releases vasopressin and oxytocin made by hypothalamic neurons. Negative feedback from the end hormone keeps each axis in balance, and most endocrine drugs either replace a missing hormone, block an excess one or use feedback on purpose.

The axes at a glance

Thyroid: TRH → TSH → T4/T3
Adrenal: CRH → ACTH → cortisol
Gonadal: GnRH → LH and FSH → testosterone, oestradiol, progesterone
Growth: GHRH (+) and somatostatin (−) → GH → IGF-1 from the liver
Prolactin: dopamine is the main brake
Posterior pituitary: vasopressin (water balance) and oxytocin (labour, milk ejection)

Using feedback in diagnosis and treatment

Hormone pairs are read together: in primary hypothyroidism TSH is high and T4 low, while in pituitary disease both are low. Levothyroxine replacement is adjusted by TSH in primary hypothyroidism. Dexamethasone suppresses ACTH in normal people but not in most ACTH-independent or ectopic cortisol excess, which makes it a diagnostic test. Metyrapone blocks cortisol synthesis and is used to treat or test the adrenal axis.

Drugs at each level

GnRH agonists (leuprorelin, goserelin): continuous exposure down-regulates the pituitary, after an initial «flare»; GnRH antagonists (degarelix) suppress at once with no flare
Somatostatin analogues (octreotide): lower GH in acromegaly and hormone release from some neuroendocrine tumours
Somatropin: recombinant GH for proven GH deficiency
Dopamine agonists (cabergoline, bromocriptine): shrink prolactinomas and lower prolactin
Desmopressin: V2 agonist for central diabetes insipidus
Oxytocin: induces or strengthens labour and prevents postpartum haemorrhage; a high-alert medicine

Suppression by treatment

Any exogenous end hormone can switch off its own axis. Glucocorticoids given for weeks or more suppress the adrenal axis, so they are tapered rather than stopped, and patients may need extra cover during illness or surgery. Excess thyroid hormone suppresses TSH; anabolic steroids and testosterone suppress LH, FSH and sperm production. Pituitary failure (hypopituitarism) is treated by replacing the end hormones, with cortisol replaced before thyroid hormone.

Test yourself

Think of the answer, then tap the question to see it.

Why does continuous leuprorelin lower testosterone even though it is a GnRH agonist?

GnRH receptors respond only to pulses; constant stimulation desensitises and down-regulates them, so LH and FSH fall after an initial flare.

Which hypothalamic signal is the main inhibitor of prolactin, and which drugs copy it?

Dopamine, acting on D2 receptors; dopamine agonists such as cabergoline and bromocriptine copy it.

Why are long courses of prednisone tapered instead of stopped abruptly?

They suppress CRH and ACTH; the adrenal glands need time to recover, and sudden withdrawal can cause adrenal insufficiency.

In hypopituitarism, why is cortisol replaced before thyroid hormone?

Thyroid hormone speeds cortisol clearance and metabolism; giving it first can precipitate an adrenal crisis when cortisol is already low.

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Example drugs

Connections

← All of pharmacology

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Hypopituitarism: MedlinePlus Medical Encyclopedia (MedlinePlus (U.S. National Library of Medicine), 2026); Pituitary & Pineal Glands (National Cancer Institute, SEER Training Modules, 2026).

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Representative model, for educational purposes only.