Regulation of the neuroendocrine reproductive axis by kisspeptin-GPR54 signaling.
The Kiss1 gene codes for a family of peptides that act as endogenous ligands for the G protein-coupled receptor GPR54. Spontaneous mutations or targeted deletions of GPR54 in man and mice produce hypogonadotropic hypogonadism and infertility. Centrally administered kisspeptins stimulate gonadotropin secretion by acting directly on GnRH neurons. Sex steroids regulate the expression of KiSS-1 mRNA in the brain through direct action on KiSS-1 neurons. In the arcuate nucleus (Arc), sex steroids inhibit the expression of KiSS-1, suggesting that these neurons serve as a conduit for the negative feedback regulation of gonadotropin secretion. In the anteroventral periventricular nucleus (AVPV), sex steroids induce the expression of KiSS-1, implying that KiSS-1 neurons in this region may have a role in the preovulatory LH surge (in the female) or sexual behavior (in the male).
Smith
Jeremy T
JT
Physiology and Biophysics and Obstetrics and Gynecology, University of Washington, Seattle, Washington 98195-7290, USA.
Clifton
Donald K
DK
Steiner
Robert A
RA
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006065:Gonadotropins, Pituitary / Q000378:metabolism; D006801:Humans; D059648:Kisspeptins; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D000074502:Receptors, Kisspeptin-1; D011966:Receptors, LHRH / Q000378:metabolism; D012098:Reproduction / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D012739:Gonadal Steroid Hormones; D006065:Gonadotropins, Pituitary; C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D011966:Receptors, LHRH; D025521:Tumor Suppressor Proteins; D007987:Gonadotropin-Releasing Hormone