Abstract:
The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) is essential for fertility in men and women. LHCGR binds luteinizing hormone (LH) as well as the highly homologous chorionic gonadotropin. Signaling from LHCGR is required for steroidogenesis and gametogenesis in males and females and for sexual differentiation in the male. The importance of LHCGR in reproductive physiology is underscored by the large number of naturally occurring inactivating and activating mutations in the receptor that result in reproductive disorders. Consequently, several genetically modified mouse models have been developed for the study of LHCGR function. They include targeted deletion of LH and LHCGR that mimic inactivating mutations in hormone and receptor, expression of a constitutively active mutant in LHCGR that mimics activating mutations associated with familial male-limited precocious puberty and transgenic models of LH and hCG overexpression. This review summarizes the salient findings from these models and their utility in understanding the physiological and pathological consequences of loss and gain of function in LHCGR signaling.
摘要:
黄体生成素/绒毛膜促性腺激素受体(LHCGR)对男性和女性的生育能力至关重要。LHCGR结合黄体生成素(LH)以及高度同源的绒毛膜促性腺激素。来自LHCGR的信号是男性和女性的类固醇生成和配子生成以及男性的性分化所必需的。LHCGR在生殖生理学中的重要性由导致生殖障碍的受体中的大量天然存在的失活和活化突变强调。因此,已经开发了几种转基因小鼠模型用于研究LHCGR功能。它们包括模拟激素和受体失活突变的LH和LHCGR的靶向缺失,LHCGR中组成型活性突变体的表达,该突变体模拟了与家族性男性限制性性早熟相关的激活突变以及LH和hCG过表达的转基因模型。这篇综述总结了这些模型的显着发现及其在理解LHCGR信号传导中功能丧失和获得的生理和病理后果方面的实用性。