A functional GnRH receptor (GnRH-R) in the anterior pituitary is critical for normal LH/FSH secretion, pubertal development and reproduction. Inactivating mutations of the GnRH-R have been identified in patients with idiopathic hypogonadotrophic hypogonadism. In this article we summarize phenotypic characteristics of these patients and focus on specific functional alterations of the human GnRH-R. In-vitro studies using recombinant receptor constructs demonstrate that GnRH-R missense mutations result in impaired ligand binding and reduced signal transduction, causing gonadotrophin deficiency. A detailed molecular understanding of receptor inactivation may help to design new GnRH agonists to therapeutically modulate GnRH-R function.

中文翻译：

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人类GnRH受体的临床和分子遗传学。

垂体前叶中的功能性GnRH受体（GnRH-R）对于正常LH / FSH分泌，青春期发育和生殖至关重要。在患有特发性性腺功能减退性性腺功能减退症的患者中已鉴定出GnRH-R的失活突变。在本文中，我们总结了这些患者的表型特征，并将重点放在人类GnRH-R的特定功能改变上。使用重组受体构建体的体外研究表明，GnRH-R错义突变导致配体结合受损和信号转导减少，从而导致促性腺激素缺乏。对受体失活的详细分子理解可能有助于设计新的GnRH激动剂来治疗性调节GnRH-R功能。