Abstract

Gonadotropin-releasing hormone (GnRH) is the central regulator of gonadotropins, which stimulate gonadal function. Hypothalamic neurons that produce kisspeptin and neurokinin B stimulate GnRH release. Inactivating mutations in the genes encoding the human kisspeptin receptor (KISS1R, formerly called GPR54), neurokinin B (TAC3), and the neurokinin B receptor (TACR3) result in pubertal failure. However, human kisspeptin loss-of-function mutations have not been described, and contradictory findings have been reported in Kiss1-knockout mice. We describe an inactivating mutation in KISS1 in a large consanguineous family that results in failure of pubertal progression, indicating that functional kisspeptin is important for puberty and reproduction in humans. (Funded by the Scientific and Technological Research Council of Turkey [TÜBİTAK] and others.).

Links

Publisher Full Text

Authors

Topaloglu AK, Tello JA, Kotan LD, Ozbek MN, Yilmaz MB, Erdogan S, Gurbuz F, Temiz F, Millar RP, Yuksel B

Institution

Faculty of Medicine, Department of Pediatric Endocrinology, Cukurova University, Adana, Turkey. ktopaloglu@cu.edu.tr

Source

The New England journal of medicine 366:7 2012 Feb 16 pg 629-35

MeSH

Adolescent
Adult
Child
Consanguinity
Female
Genes, Recessive
Genotyping Techniques
Gonadotropin-Releasing Hormone
Humans
Hypogonadism
Kisspeptins
Male
Mutation
Pedigree
Puberty
Sequence Analysis, DNA

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22335740