Teles Milena Gurgel, Bianco Suzy D C, Brito Vinicius Nahime, Trarbach Ericka B, Kuohung Wendy, Xu Shuyun, Seminara Stephanie B, Mendonca Berenice B, Kaiser Ursula B, Latronico Ana Claudia
Developmental Endocrinology Unit, Medical Investigation Laboratory, Clinicas Hospital, São Paulo University Medical School, São Paulo.
N Engl J Med. 2008 Feb 14;358(7):709-15. doi: 10.1056/NEJMoa073443.
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.
促性腺激素依赖性或中枢性性早熟是由下丘脑 - 垂体 - 性腺轴过早成熟引起的。在女孩中，这种情况最常见的是特发性的。最近，一种G蛋白偶联受体GPR54及其配体 kisspeptin被描述为促性腺激素释放激素（GnRH）分泌的兴奋性神经调节系统。在本研究中，我们在一名患有特发性中枢性性早熟的领养女孩（其生物学家族无法进行基因研究）中鉴定出一种常染色体显性GPR54突变——密码子386处脯氨酸替代精氨酸（Arg386Pro）。体外研究表明，这种突变导致细胞内信号通路在 kisspeptin作用下的持续激活。Arg386Pro突变体似乎与中枢性性早熟有关。
