[Kisspeptin and leptin in the regulation of fertility].
Kisspeptin (KISS1) and its receptor (KISS1R) are important regulators of the reproductive function, along with gonadoliberin (GnRH), gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)), and sex steroid hormones. Mutations of their genes alter sexual maturation. The p.P74S, p.H90D, and p.P110T missense mutations of KISS1 are associated with central precocious puberty (CPP); and the p.G35S, p.C53R, and p.F117L mutations, with delayed puberty and isolated hypogonadotropic hypogonadism (IHH). The p.P196H and p.R386P mutations of KISS1R are also associated with CPP. However, a greater number of KISS1R mutations are associated with IHH, as is the case with p.L102P, p.L148S, p.E232Q, p.R297L, p.Y313H, pX399R, and more complex mutations, such as the 155-bp deletion that removes the acceptor splice site of intron 4 and part of exon 5, a deletion of the GCA triplet in position-2 ...-4 of intron 2, and an ACCGGCT insertion in the same site. The heterozygous compound mutations p.C223R/p.R297L and p.R331X/X399R and the 1-bp insertion 1001_1002insC of KISS1R are similarly associated with IHH. Leptin-dependent activation of KISS1 in hypothalamic neurons was observed in mice and sheep, being especially evident after puberty. Leptin exerts a permissive effect in regulating fertility and facilitate the induction of puberty by hypothalamic KISS1 and GnRH and pituitary LH and FSH, which support the reproductive function during further life.
Endocrinology Research Center, Ministry of Health of the Russian Federation, Moscow, 115778, Russia.|pankov.yuriy@endocrincentr.ru.
Yu A
YA
Pankov
D005298:Fertility / Q000235:genetics*; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D012739:Gonadal Steroid Hormones / Q000235:genetics / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059648:Kisspeptins / Q000235:genetics* / Q000378:metabolism; D020738:Leptin / Q000235:genetics* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011629:Puberty, Precocious / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D012741:Sexual Maturation / Q000235:genetics; D015398:Signal Transduction
D012739:Gonadal Steroid Hormones; C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D020738:Leptin; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
Gene; hormone; mutation; puberty onset; pulse secretion; receptor