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Previous Volume 358:709-715 February 14, 2008 Number 7 Next

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SUMMARY

Gonadotropin-dependent, or central, precocious puberty is caused by early maturation of the hypothalamic–pituitary–gonadal axis. In girls, this condition is most often idiopathic. Recently, a G protein–coupled receptor, GPR54, and its ligand, kisspeptin, were described as an excitatory neuroregulator system for the secretion of gonadotropin-releasing hormone (GnRH). In this study, we have identified an autosomal dominant GPR54 mutation — the substitution of proline for arginine at codon 386 (Arg386Pro) — in an adopted girl with idiopathic central precocious puberty (whose biologic family was not available for genetic studies). In vitro studies have shown that this mutation leads to prolonged activation of intracellular signaling pathways in response to kisspeptin. The Arg386Pro mutant appears to be associated with central precocious puberty.

Source Information

From the Developmental Endocrinology Unit, Medical Investigation Laboratory, Clinicas Hospital, São Paulo University Medical School, São Paulo (M.G.T., V.N.B., E.B.T., B.B.M., A.C.L.); and the Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital (M.G.T., S.D.C.B., W.K., S.X., U.B.K.); Harvard Reproductive Endocrine Sciences Center (M.G.T., S.D.C.B., W.K., S.X., S.B.S., U.B.K.); Boston University School of Medicine (W.K.); and the Reproductive Endocrine Unit, Massachusetts General Hospital (S.B.S.) — all in Boston.

Drs. Teles and Bianco contributed equally to this article, as did Drs. Kaiser and Latronico.

Address reprint requests to Dr. Latronico at the Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Disciplina de Endocrinologia e Metabologia, Av. Dr. Eneas de Carvalho Aguiar, 155–2° andar Bloco 6, 05403-900 São Paulo, Brazil, or at anacl{at}usp.br.

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