GnRH

GnRH, or gonadotropin-releasing hormone, is a hypothalamic decapeptide that governs vertebrate reproduction by regulating the anterior pituitary's secretion of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In mammals, GnRH is encoded by the GNRH1 gene, synthesized as a larger precursor, and processed to the active decapeptide, whose amino acid sequence is pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2.

GnRH is released into the hypophyseal portal circulation in a pulsatile manner. Binding to GnRH receptors, a G protein-coupled receptor on pituitary gonadotrophs, stimulates intracellular signaling that triggers episodic LH and FSH secretion. The frequency and pattern of GnRH pulses influence the ratio of LH to FSH release, with high-frequency stimulation favoring LH and lower frequency favoring FSH.

Physiologically, GnRH drives sexual maturation and reproduction. In males, LH stimulates Leydig cells to produce testosterone, while FSH supports spermatogenesis with Sertoli cells. In females, FSH promotes follicular development and estrogen production, and the LH surge triggers ovulation and luteinization with progesterone production by the corpus luteum. GnRH secretion is under negative feedback from sex steroids and inhibin, modulating reproductive axis activity.

Clinically, synthetic GnRH analogs are used to manipulate the reproductive axis. GnRH agonists (for example, leuprolide) initially stimulate, then downregulate GnRH receptors and suppress gonadotropin release; they are used in hormone-sensitive cancers, endometriosis, precocious puberty, and assisted reproduction. GnRH antagonists (such as ganirelix, cetrorelix) rapidly block GnRH receptors and are employed to prevent premature LH surges during controlled ovarian stimulation.