GnRH-GnRH-Receptor System in the Mammalian Female Reproductive Tract

Reproduction in mammals is controlled by interactions between the hypothalamus, anterior pituitary, and gonads. The hypothalamus secretes synchronized pulses of gonadotropin-releasing hormone (GnRH) as the central initiator of the reproductive hormonal cascade from the diffusely arranged network of neuronal nerve endings of about 800 (rodents) to 1,500–2,000 (human) into the hypophyseal portal system every 30–120 min. GnRH stimulates the biosynthesis and secretion of the gonadotropic hormones, LH, and FSH by the anterior pituitary that in turn regulate the production of gametes and gonadal hormones as a key regulator of the reproductive functions. In the 1970 s, GnRH was first isolated from hypothalamus of pigs and sheep, and the subsequent realization that the decapeptide sequence was conserved across all mammals. This form of GnRH is referred as GnRH-I or type I mammalian GnRH (mGnRH). In 1977, Andrew Schally, Roger Guillemin, and co-workers shared the Nobel Prize in the field of Medicine for their discovery. In the early 1980 s, a second GnRH isoform from chickens was isolated (chicken GnRH; GnRH-II) [1] and a third isoform was identified in fish (salmon GnRH) [2]. Currently, a total of 23 different isoforms of chordate GnRH have been isolated [3–5]. All of these isoforms are decapeptides that share a high degree of sequence identity at both NH₂- and COOH-terminals. This overview describes the recent literature regarding the GnRH primary structure, tissue distribution in female reproductive system, synthesis, secretion, and signaling pathways with current understanding on their cognate receptors and functional significance in relation to female reproductive system.