Gonadotropin-releasing hormone (GnRH)
Also known as: GnRH, LHRH, gonadoliberin
A decapeptide released in pulses (every ≈60–120 min) from hypothalamic neurons that stimulates LH and FSH secretion; pulsatility is essential — continuous GnRH shuts the axis down.
Overview
GnRH neurons are unusual: they originate in the olfactory placode and migrate into the forebrain during embryonic life, settling mainly in the preoptic area and mediobasal hypothalamus (arcuate region), with terminals in the median eminence. Their output is pulsatile, driven by the arcuate KNDy neurons (kisspeptin stimulates via the GPR54/KISS1R receptor; neurokinin B and dynorphin shape the pulses).
At gonadotrophs GnRH binds a Gq-coupled receptor (IP₃/Ca²⁺, DAG/PKC). Pulse frequency encodes the output: faster pulses (≈hourly) favour LH, slower pulses favour FSH — the luteal phase slowing of pulses by progesterone promotes FSH rise for the next cycle, while persistently rapid pulses in PCOS favour LH excess. Sustained, non-pulsatile exposure desensitises and down-regulates the receptor.
The GnRH pulse generator is active in fetal and early infant life ("mini-puberty"), is suppressed through childhood, and is reactivated at puberty, initially with nocturnal pulses.
- Location
Source: preoptic area and arcuate (infundibular) region → median eminence. Target: gonadotrophs of the anterior pituitary.
Function
- Stimulates synthesis and pulsatile release of LH and FSH.
- Initiates and maintains puberty and reproductive function.
- Physiology
Class: decapeptide. Receptor: GnRHR (Gq → IP₃/Ca²⁺, DAG/PKC). Half-life ≈2–4 min. Pulse frequency ≈every 60–120 min (faster in the follicular, slower in the luteal phase).
- Regulation
Stimulated by kisspeptin, adequate leptin/energy stores; inhibited by sex steroids (negative feedback, partly via KNDy neurons), progesterone (slows pulses), prolactin, CRH/cortisol, opioids and energy deficit. In the late follicular phase high estradiol switches to positive feedback, amplifying GnRH and pituitary responsiveness to produce the LH surge.
Clinical significance
GnRH analogues
Long-acting agonists (leuprorelin, goserelin, triptorelin) given continuously cause an initial flare, then down-regulation and "medical castration" — used for prostate and breast cancer, endometriosis, fibroids, central precocious puberty and IVF protocols. Antagonists (degarelix, cetrorelix, elagolix) suppress immediately without flare. Pulsatile GnRH by pump restores fertility in hypothalamic amenorrhoea.
Functional hypothalamic amenorrhoea
Energy deficit, excessive exercise or stress (low leptin, raised cortisol) slows GnRH pulses → low LH/FSH and estradiol, amenorrhoea and bone loss (female athlete triad / relative energy deficiency in sport).
Kallmann syndrome
Failure of GnRH neuron migration with anosmia; congenital hypogonadotropic hypogonadism.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.