GonadotropinReleasing

Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide that regulates the pituitary-gonadal axis. In humans, GnRH is produced by neurons in the arcuate nucleus and other hypothalamic regions and released into the portal circulation to the anterior pituitary, where it binds GnRH receptors on gonadotrophs to stimulate the synthesis and pulsatile secretion of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

GnRH is released in regular bursts; the frequency and amplitude of pulses influence the relative secretion of LH and FSH. Prolonged, continuous exposure to GnRH or its agonists leads to receptor downregulation and suppression of LH and FSH, a property exploited in several clinical contexts.

Physiologically, LH and FSH regulate gonadal steroidogenesis and gametogenesis, supporting puberty, fertility, and reproductive health. LH stimulates testosterone production in males and ovulation with subsequent progesterone production in females, while FSH supports spermatogenesis and follicular development.

Clinical uses and pharmacology: Pulsatile GnRH administration is used to treat certain forms of hypogonadotropic hypogonadism and infertility by restoring endogenous gonadotropin release. Synthetic GnRH analogs are used to control the reproductive axis in conditions such as endometriosis, uterine fibroids, precocious puberty, and hormone-sensitive cancers (notably prostate cancer). GnRH agonists initially stimulate, then suppress, gonadotropin release with continued use, whereas GnRH antagonists provide rapid suppression without an initial rise in gonadotropins.

Administration varies by formulation and can include injections or, for some preparations, nasal delivery. Side effects generally reflect reduced sex hormone levels and may include hot flashes, reduced libido, bone density loss with long-term use, and injection-site reactions.