Kisspeptin and GPR54: discovery of a novel pathway in reproduction.
In order to find novel modulators of gonadotrophin-releasing hormone (GnRH) secretion, genetic tools were employed in patients with idiopathic hypogonadotrophic hypogonadism (IHH). Mutations in a G-protein coupled receptor, GPR54, were identified, making this receptor a genetic determinant and indisputable gatekeeper of normal reproductive function. This article places these investigations into historical context and reviews some of the new findings relevant to this pathway.
Seminara
S B
SB
Reproductive Endocrine Unit, Harvard Partners Reproductive Sciences Centre, Massachusetts General Hospital, Boston, MA 02114, USA. sseminara@partners.org
Crowley
W F
WF
D000818:Animals; D017353:Gene Deletion; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000235:genetics / Q000378:metabolism; D059648:Kisspeptins; D011627:Puberty / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D000074502:Receptors, Kisspeptin-1; D012098:Reproduction / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D025521:Tumor Suppressor Proteins; D007987:Gonadotropin-Releasing Hormone; D020962:Heterotrimeric GTP-Binding Proteins