GnRH (Gonadotropin-Releasing Hormone)

Hormonal / Reproductive

Also known as: Gonadotropin-Releasing Hormone, GnRH-I, LHRH, Luteinizing Hormone-Releasing Hormone, Gonadorelin Endogenous

Hypothalamic Releasing HormonesResearch phase: Endogenous hormone (well characterized)Regulatory: Endogenous peptide. Synthetic form (gonadorelin) is FDA-approved as a diagnostic agent.

Mechanism

GnRH is the master reproductive hormone, a 10-amino-acid peptide released in pulses from the hypothalamus. It travels to the pituitary gland where it triggers the release of LH and FSH — the hormones that control testosterone production in men and ovulation in women. Its pulsatile release pattern is critical: continuous GnRH actually shuts down reproduction, which is how GnRH agonist drugs work.

Technical detail

GnRH (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) is a hypothalamic decapeptide released in pulsatile fashion from GnRH neurons in the arcuate nucleus. It binds GnRHR (a Gq-coupled GPCR) on anterior pituitary gonadotrophs, activating PLC-IP3-DAG-PKC signaling to stimulate LH and FSH synthesis and secretion. Pulsatile release (every 60-120 min) maintains gonadotroph sensitivity, while continuous exposure causes receptor downregulation and gonadotropin suppression (basis for GnRH agonist therapy). KNDy neurons (kisspeptin/neurokinin B/dynorphin) regulate GnRH pulse generation.

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