Prolactin Physiology
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Direct answer
Prolactin, a 198-199 amino acid anterior pituitary hormone from lactotrophs, is the only adenohypophyseal hormone under net tonic inhibition — hypothalamic dopamine acting through D2 receptors on the portal system — so anything that removes dopamine (drugs, stalk compression, suckling) raises it. Basal levels are roughly 5-25 ng/mL, rising through pregnancy to 100-200 ng/mL or more at term under oestrogen-driven lactotroph hyperplasia, and surging with each feed thereafter. Suckling is a true neuroendocrine reflex: nipple stimulation through intercostal afferents reaches the hypothalamus, which briefly lifts dopamine inhibition, releasing a prolactin pulse that manufactures the next meal while oxytocin ejects the current one. Sustained hyperprolactinaemia above about 25 ng/mL suppresses GnRH pulsatility — galactorrhoea with amenorrhoea and infertility — and dopamine agonists (cabergoline, bromocriptine) are the logical treatment.
What you must remember
- Unique control: tonic inhibition by dopamine (prolactin-inhibiting factor) via D2 receptors — the inverse of every other anterior pituitary hormone; hypothalamic stalk section raises prolactin while lowering the rest.
- Stimuli: suckling (chief), oestrogen, TRH (why hypothyroidism causes galactorrhoea), stress, sleep, exercise, and chest wall stimulation — the latter mimicking suckling through intercostal afferents.
- Levels to quote: non-pregnant women about 5-25 ng/mL, men slightly lower; pregnancy climbs to 100-200 ng/mL or more; prolactinoma macroadenoma can exceed 200 ng/mL with levels generally paralleling tumour size.
- Suckling reflex arc: nipple, intercostal nerves 4-5, hypothalamus, withdrawal of dopamine, lactotroph prolactin release — an afferent neural limb with an efferent hormonal limb, the definition of a neuroendocrine reflex.
- Lactational amenorrhoea: suckling-driven prolactin suppresses GnRH pulsatility; exclusive breastfeeding with absent menses in the first six months is the basis of the lactational amenorrhoea method of contraception, quoted at about 98 per cent effective when criteria are strictly met.
- Drug causes: D2 blockers (haloperidol, risperidone, metoclopramide, domperidone) and, to a lesser degree, SSRIs and oestrogens; the viva rule is that any dopamine antagonist is a prolactin raiser.
- Non-lactational roles: lymphocyte proliferation factor, component of the immune system, and decidua-derived prolactin in amniotic fluid — decidua synthesises it independent of hypothalamic control.
- Hyperprolactinaemia work-up: serum prolactin, TSH (primary hypothyroidism mimics), and MRI for macroadenoma (>10 mm); macroprolactin (the big-big complex) is a benign assay artefact worth excluding before labelling disease.
A worked case in amenorrhoea
A 28-year-old woman presents with six months of amenorrhoea, milky nipple discharge and headaches. The sequence writes itself: elevated prolactin (say 120 ng/mL) suppresses hypothalamic GnRH, so LH pulses flatten, ovulation ceases, the luteal phase fails, and oestrogen falls — amenorrhoea with low bone-protective steroids. The discharge is prolactin-driven ductal secretion. The headache raises the stakes: MRI shows a 14 mm macroadenoma, and the visual field chart confirms a bitemporal superior quadrantanopia from chiasmal compression.
Physiology dictates therapy: restore dopaminergic inhibition. Cabergoline activates D2 receptors on the lactotroph, shrinking the adenoma and normalising prolactin in most patients, restoring cycles and fertility — and it is stopped once pregnancy is confirmed unless the tumour is large. Contrast the mimic: a woman with primary hypothyroidism, raised TRH, modest hyperprolactinaemia and menorrhagia — her levothyroxine alone cures the discharge, and treating her with a dopamine agonist would mask the thyroid disease. Always send TSH with the first prolactin.
Where students slip
The first slip is mechanical: students draw all pituitary hormones under releasing-hormone control and place prolactin symmetrically under a prolactin-releasing factor — the dominant control is inhibitory, dopamine, and stalk effect raises prolactin. The second is separating the two hormones of breastfeeding: prolactin makes milk (secretion), oxytocin delivers it (ejection) — the let-down reflex has oxytocin written on it, and mixing the two loses the easiest viva mark of the topic. Third, forgetting that bromocriptine and ergot-derived agonists are stopped in pregnancy while cabergoline may be continued for large tumours — a management nuance examiners increasingly ask.
Frequently asked questions
Why is prolactin unique among anterior pituitary hormones?
It is under tonic inhibitory control by hypothalamic dopamine through D2 receptors, so pituitary stalk section or dopamine antagonists increase prolactin secretion while all other anterior pituitary hormones fall.
What is the suckling reflex arc?
Afferent impulses from the nipple travel through intercostal nerves to the hypothalamus, which withdraws dopamine inhibition; the resulting prolactin pulse promotes milk synthesis while a simultaneous oxytocin release ejects milk.
How does hyperprolactinaemia cause amenorrhoea?
Excess prolactin suppresses hypothalamic GnRH pulsatility, flattening LH and FSH secretion, abolishing ovulation and producing hypo-oestrogenic amenorrhoea with infertility.
Which drugs commonly raise prolactin?
Dopamine D2 receptor antagonists — metoclopramide, domperidone, haloperidol, risperidone — plus oestrogens and some SSRIs; the mechanism is loss of tonic dopaminergic inhibition of lactotrophs.
Why is TSH checked in every new galactorrhoea?
Primary hypothyroidism raises TRH, which stimulates lactotrophs and mimics prolactinoma; treating the thyroid disorder resolves the hyperprolactinaemia without dopamine agonists.