GnRHsignaler

GnRH signaling refers to the cellular processes triggered when gonadotropin-releasing hormone (GnRH) binds to the GnRH receptor (GNRHR) on pituitary gonadotrophs. GnRH is produced in the hypothalamus and released into the hypophyseal portal circulation in a pulsatile manner, with pulse patterns encoding different endocrine outputs. GNRHR is a class A G protein-coupled receptor that primarily couples to Gq/11 proteins. Upon GnRH binding, phospholipase Cβ is activated, leading to hydrolysis of PIP2 into IP3 and DAG. IP3 stimulates intracellular Ca2+ release, while DAG activates protein kinase C. The rise in intracellular Ca2+ triggers exocytosis of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Additionally, GnRH signaling activates mitogen-activated protein kinase (MAPK) and other pathways that influence gene expression of gonadotropin subunits and other regulators.

The pattern of GnRH stimulation regulates LH and FSH release: high-frequency pulses favor LH, while low-frequency pulses favor FSH. Continuous exposure to GnRH (as with chronic GnRH agonist therapy) leads to receptor desensitization and suppression of gonadotropin secretion due to receptor internalization and downregulation.

Beyond the pituitary, GnRH receptors have been reported in various tissues, suggesting autocrine/paracrine roles in development and possibly in certain cancers. Clinically, GnRH agonists and antagonists are used to manipulate the hypothalamic-pituitary-gonadal axis in fertility treatment, hormone-sensitive cancers, endometriosis, and precocious puberty.