Obstetrics and Gynaecology chapters
Reproductive hormones: hypothalamus, pituitary, thyroid, gonads and prolactin
How the hypothalamus, pituitary, thyroid, parathyroid and gonads talk to each other through feedback loops, and how prolactin and oxytocin control milk production and let-down.
- The hypothalamus releases GnRH in pulses; pulses drive FSH and LH, while a continuous supply switches the pituitary off.
- Ovarian steroids mostly give negative feedback, but sustained high oestradiol gives positive feedback and the LH surge; inhibin selectively lowers FSH.
- Prolactin is under tonic dopamine inhibition; suckling raises prolactin (milk production) and oxytocin (milk ejection).
On this page
Overview
Reproduction is run by a chain of glands: hypothalamus → anterior pituitary → ovary (or testis) → target organs. Each level is controlled by hormones from the level above and checked by feedback from the level below. The same pattern runs the thyroid and adrenal glands.
For the PGET exam you need to know three things well:
- How GnRH, FSH and LH work and why the pattern of GnRH release matters.
- The feedback rules for oestrogen, progesterone and inhibin, including the one switch to positive feedback.
- How prolactin is controlled and how milk is made and released.
The hypothalamus and pituitary
- Hypothalamic releasing hormones reach the anterior pituitary through the hypophyseal portal veins.
- The posterior pituitary stores oxytocin and ADH, made in hypothalamic neurons.
- Anterior pituitary hormones relevant here: FSH, LH, TSH, ACTH, prolactin, growth hormone.
The hypothalamus mostly stimulates the anterior pituitary. Prolactin is the exception: it is held down by dopamine. So if the stalk is cut or compressed, prolactin rises while the other anterior pituitary hormones fall.
GnRH
- A decapeptide made mainly in the arcuate nucleus of the mediobasal hypothalamus.
- Released in pulses, roughly one every 1-2 hours; each pulse gives a pulse of LH.
- Pulsatile GnRH keeps the pituitary receptors responsive. A constant supply (as with a depot GnRH agonist) first gives a brief rise ("flare"), then downregulates the receptors, so FSH, LH and oestradiol fall. This is how GnRH agonists treat endometriosis, fibroids and precocious puberty.
- Pulse frequency matters: faster pulses favour LH; slower pulses favour FSH. Persistently fast pulses are part of the high LH:FSH ratio of PCOS.
- Kisspeptin neurons drive GnRH neurons. Leptin from fat signals energy stores to this system, which is why low body weight stops periods and delays puberty.
- Stress (CRH, cortisol), opioids and high prolactin all slow GnRH pulses.
A GnRH agonist and a GnRH antagonist both end up lowering FSH and LH. The agonist does it by desensitisation after an initial flare; the antagonist blocks the receptor at once with no flare.
FSH and LH
FSH, LH, TSH and hCG are glycoproteins with a shared alpha subunit. The beta subunit gives each its own receptor and is what specific assays measure. hCG is so similar to LH that it acts on the LH receptor (used as the ovulation "trigger" in IVF).
The two-cell, two-gonadotrophin model
| Cell | Hormone acting on it | What it does |
|---|---|---|
| Theca cell | LH | Makes androgens (androstenedione, testosterone) from cholesterol |
| Granulosa cell | FSH | Aromatase converts those androgens to oestradiol; also makes inhibin and AMH |
| Granulosa cell (late follicular) | FSH then LH | FSH induces LH receptors on granulosa cells of the dominant follicle; after the LH surge they luteinise and make progesterone |
In the male: LH → Leydig cells → testosterone; FSH → Sertoli cells → spermatogenesis support, inhibin B and androgen-binding protein.
Feedback rules
| Signal | Effect on pituitary | When it matters |
|---|---|---|
| Low or moderate oestradiol | Negative feedback on FSH and LH | Most of the cycle; the basis of the combined pill |
| High oestradiol held for about 2 days | Positive feedback: LH surge (and a smaller FSH rise) | Late follicular phase, triggers ovulation |
| Low progesterone (after oestrogen priming) | Adds to the positive feedback | Just before ovulation |
| High progesterone | Negative feedback; slows GnRH pulses | Luteal phase |
| Inhibin (granulosa cells, corpus luteum) | Mainly lowers FSH | Selects one dominant follicle; inhibin B falls with ageing |
| Activin | Raises FSH action | Local (paracrine) role |
The combined oral contraceptive pill keeps oestrogen in the negative feedback range all month, so no LH surge and no ovulation.
"Low and steady says no; high and held says go" for oestradiol feedback.
Gonadal steroids
Oestrogens
- Oestradiol is the main ovarian oestrogen and the most potent.
- Oestrone is weaker; much of it is made in fat by aromatisation of adrenal androstenedione. It is the main oestrogen after the menopause (relevant to obesity and endometrial cancer).
- Oestriol is the weakest; it is the main oestrogen of pregnancy, made by the placenta from fetal adrenal precursors.
- Oestradiol is about 12 times as potent as oestrone and 80 times as potent as oestriol.
Progesterone
- Made by the corpus luteum in the luteal phase and by the placenta in pregnancy.
- Broken down in the liver to pregnanediol, which appears in urine (used in home ovulation monitors).
- Raises basal body temperature slightly after ovulation.
Androgens in women
- Come from the ovarian theca and stroma, the adrenals and peripheral conversion of androstenedione. The ovaries go on making some androgen after the menopause.
Transport and breakdown
- Carried bound to albumin and sex hormone-binding globulin (SHBG); only the unbound part is active.
- SHBG is raised by oestrogen (and the pill) and lowered by insulin and androgens. That is why obese insulin-resistant women with PCOS have low SHBG and more active testosterone.
- The liver conjugates and clears steroids; liver failure raises oestrogen effect.
Actions compared
| Target | Oestrogen | Progesterone |
|---|---|---|
| Endometrium | Proliferation (glands and stroma) | Secretory change, decidualisation; stops further growth |
| Cervical mucus | Thin, watery, stretchy (lets sperm in) | Thick, scanty (blocks sperm) |
| Myometrium | Growth | Relaxes (keeps pregnancy quiet) |
| Breast | Duct growth, fat deposition | Lobule and alveolar development |
| Vagina | Stratified epithelium, glycogen | - |
| Bone | Inhibits osteoclasts; closes epiphyses | - |
| Liver | Raises SHBG, TBG and clotting factors | - |
| Body temperature | - | Raises it slightly |
Anti-Müllerian hormone (AMH)
- In the male fetus, AMH from Sertoli cells makes the Müllerian ducts regress.
- In the adult woman, AMH comes from granulosa cells of small growing follicles. It barely changes through the cycle, so it can be checked on any day. It is the best blood marker of ovarian reserve: high in PCOS, low as menopause nears.
Thyroid and parathyroid
Thyroid axis
- TRH → TSH → T4 and T3; T4 and T3 feed back negatively on both the hypothalamus and the pituitary.
- Most hormone is bound to thyroxine-binding globulin (TBG); oestrogen and pregnancy raise TBG, so total T4 rises while unbound T4 stays near normal. In pregnancy measure FT4 and TSH, not total hormone.
- In early pregnancy hCG weakly stimulates the TSH receptor: TSH falls and FT4 rises in the first trimester (more so in hyperemesis and molar pregnancy).
- Primary hypothyroidism raises TRH, which also stimulates prolactin; this can cause galactorrhoea, irregular periods and subfertility.
Parathyroid hormone (PTH)
- Released when ionised calcium falls. It raises calcium by bone resorption, renal calcium reabsorption and activation of vitamin D.
- In pregnancy and lactation, the fetus and baby take large amounts of calcium; maternal parathyroid activity rises, especially if dietary calcium is poor. Vitamin D is needed for calcium absorption.
Prolactin
Control
- Made by lactotrophs of the anterior pituitary.
- Held down tonically by dopamine from tuberoinfundibular neurons of the arcuate nucleus, acting on D2 receptors.
- Raised by TRH, oestrogen, suckling, stress and sleep.
Causes of high prolactin
| Group | Examples |
|---|---|
| Physiological | Pregnancy, breastfeeding, stress (even a difficult blood test), sleep |
| Drugs (block dopamine or deplete it) | Antipsychotics (risperidone, haloperidol), metoclopramide, domperidone, methyldopa, opioids |
| Pituitary | Prolactinoma (commonest pituitary adenoma); large tumours compressing the stalk |
| Hypothalamic | Craniopharyngioma, infiltration, stalk injury |
| Other | Primary hypothyroidism, chronic renal failure (reduced clearance), chest wall lesions (shingles, surgery) |
| Lab | Macroprolactin (prolactin-antibody complex, inactive) |
Effects and treatment
- High prolactin slows GnRH pulses: low FSH, LH and oestradiol, giving oligomenorrhoea or amenorrhoea, subfertility and, if long-standing, bone loss.
- Galactorrhoea; a macroadenoma also causes headache and bitemporal visual field loss.
- Treatment is a dopamine agonist (cabergoline or bromocriptine); surgery if drugs fail.
A very large pituitary tumour with only a mildly raised prolactin may be a non-secreting tumour compressing the stalk, not a prolactinoma. The two need different treatment.
Lactation
Breast development (mammogenesis)
- Oestrogen: growth and branching of the ducts, plus fat.
- Progesterone: development of lobules and alveoli.
- Growth hormone, cortisol, insulin, prolactin and human placental lactogen help.
Why milk waits until after birth
- Prolactin rises from early pregnancy to about 10-20 times normal at term.
- But high placental oestrogen and progesterone block milk secretion, so only small volumes of colostrum are made.
- When the placenta is delivered, these steroids fall quickly and prolactin can act; full milk production starts over the next few days.
Retained placental tissue keeps progesterone up and can delay milk coming in.
Colostrum
- Can be expressed from about mid-pregnancy; replaced by milk in the first few days after birth.
- Richer in protein (mainly IgA) than mature milk, with less sugar and fat.
The suckling reflex
| Pathway | Hormone | Result |
|---|---|---|
| Nipple → hypothalamus → less dopamine | Prolactin (anterior pituitary) surges for about an hour | Milk production for the next feed |
| Nipple → hypothalamus → paraventricular and supraoptic nuclei | Oxytocin (posterior pituitary) | Myoepithelial cells contract: milk ejection (let-down) |
- Let-down can be triggered by hearing or seeing the baby; stress, pain and fear inhibit oxytocin and let-down.
- Milk left in the breast locally suppresses further production, so frequent emptying keeps supply up.
- Suckling also suppresses GnRH pulses, so breastfeeding delays the return of ovulation (lactational amenorrhoea). This is not reliable once feeds become less frequent.
After massive postpartum haemorrhage, failure to lactate is often the first sign of pituitary necrosis (Sheehan syndrome), followed later by amenorrhoea and other pituitary failure.
Expect: pulsatile versus continuous GnRH and how GnRH agonists and antagonists work; LH on theca and FSH on granulosa (aromatase); the switch of oestradiol to positive feedback for the LH surge; inhibin and FSH; AMH as a marker of ovarian reserve; the shared alpha subunit of LH, FSH, TSH and hCG; prolactin under dopamine inhibition, causes of hyperprolactinaemia (drugs, hypothyroidism, stalk section) and treatment with cabergoline; why milk is blocked in pregnancy; prolactin for production and oxytocin for ejection; Sheehan syndrome presenting with failure to lactate.
Quick revision
- GnRH: decapeptide, arcuate nucleus, pulses every 1-2 hours; continuous supply desensitises.
- LH → theca → androgens; FSH → granulosa → aromatase → oestradiol.
- Oestradiol: negative feedback except when high and sustained (LH surge).
- Inhibin lowers FSH; AMH reflects ovarian reserve.
- SHBG up with oestrogen, down with insulin and androgens.
- Prolactin: dopamine inhibits, TRH and oestrogen stimulate; stalk section raises it.
- Pregnancy: high prolactin but milk blocked by oestrogen and progesterone.
- Suckling: prolactin (make milk) and oxytocin (eject milk).
Written by The House Job from standard references (Gynaecology by Ten Teachers; Obstetrics by Ten Teachers; Guyton and Hall Textbook of Medical Physiology).
FAQ
Why do GnRH agonists cause a "medical menopause"?
Given continuously, they overstimulate and then downregulate the pituitary GnRH receptors, so FSH, LH and ovarian oestrogen fall after a short initial flare.
Why does hypothyroidism cause galactorrhoea?
Low thyroid hormone raises hypothalamic TRH, and TRH stimulates lactotrophs as well as thyrotrophs, so prolactin rises.
Why does breastfeeding delay periods?
Suckling and the prolactin it produces slow GnRH pulses, so FSH and LH stay low and follicles do not mature; protection fades as feeds become less frequent.
What is the difference between prolactin and oxytocin in lactation?
Prolactin from the anterior pituitary drives milk synthesis; oxytocin from the posterior pituitary contracts myoepithelial cells to push milk into the ducts.