Physiology, Gonadotropin-Releasing Hormone

Excerpt

Gonadotropin-releasing hormone (GnRH), a decapeptide, is a part of the hypothalamic-pituitary-gonadal axis, and being a part of this system makes it vital for human reproduction. Since its discovery by a group of Nobel laureate Andrew V. Schally in 1971 from porcine hypothalamus as one of the earliest hypothalamic releasing hormones, it has been a center of attention of research scientists because of its central role in reproduction not only in humans but also in all vertebrates.

Over 20 different primary structures of GnRH and its receptors have been studied across different species. Compared to GnRH I, GnRH II is not widely distributed. It is found in the central nervous system, where it seems to act as a neuromodulator of sexual behavior and in the tissues of the female reproductive system, such as the endometrium, ovary, and placenta (and in tumors derived from these tissues). GnRH I & II are present in humans, GnRH-I (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly·NH2) is mainly discussed in this review because it is the main isoform having the most physiologic importance in humans.

Gonadotropin-releasing hormone (GnRH) is a crucial substance in the hypothalamic-pituitary-gonadal (HPG) axis in humans. Production of GnRH occurs in the neurons of the hypothalamus and causes the downstream production of sex hormones by the gonads. This hormone ultimately regulates puberty onset, sexual development, and ovulatory cycles in females. Intrinsic or extrinsic disruptions in this pathway can lead to the development of pathologic conditions in humans. Pharmacologic analogs of GnRH are useful in the treatment of gynecological disease due to their ability to block estrogen secretion from the ovary. Emerging evidence suggests that stimulation of tumor GnRH receptors induces antiproliferative and antimetastatic activity, making it a potential therapeutic target. This review will discuss the cellular and genetic characteristics of GnRH as well as its physiologic and pathophysiologic mechanisms in humans.