Departments of Obstetrics/Gynecology and Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0617, United States.
Mol Cell Endocrinol. 2012 Jun 5;356(1-2):88-97. doi: 10.1016/j.mce.2012.01.021. Epub 2012 Feb 9.
Luteinizing hormone receptor and follicle stimulating hormone receptor play a crucial role in female and male reproduction. Significant new information has emerged about the structure, mechanism of activation, and regulation of expression of these receptors. Here we provide an overview of the current information on those aspects with an in-depth discussion of the recent developments in the post-transcriptional mechanism of LH receptor expression mediated by a specific LH receptor mRNA binding protein, designated as LRBP. LRBP was identified by electrophoretic gel mobility shift assay using cytosolic fractions from ovaries in the down regulated state. LRBP was purified, its binding site on LH receptor mRNA was identified and characterized. During ligand-induced down regulation, LRBP expression is increased through the cAMP/PKA and ERK signaling pathway, is translocated to translating ribosomes, binds LH receptor mRNA and forms an untranslatable ribonucleoprotein complex. This complex is then routed to the mRNA degradation machinery resulting in diminished levels of both LHR mRNA and cell surface expression of LH receptor. The studies leading to these conclusions are presented.
黄体生成素受体和卵泡刺激素受体在女性和男性生殖中起着至关重要的作用。关于这些受体的结构、激活机制和表达调控,已经有了重要的新信息。在这里,我们提供了关于这些方面的最新信息概述,并深入讨论了最近在黄体生成素受体表达的转录后机制方面的发展,该机制由一种特定的黄体生成素受体 mRNA 结合蛋白(称为 LRBP)介导。LRBP 是通过使用处于下调状态的卵巢细胞浆部分的电泳凝胶迁移率变动分析鉴定的。LRBP 被纯化,其在黄体生成素受体 mRNA 上的结合位点被鉴定并进行了特征描述。在配体诱导的下调过程中,LRBP 的表达通过 cAMP/PKA 和 ERK 信号通路增加,被转位到翻译核糖体上,与黄体生成素受体 mRNA 结合形成不可翻译的核糖核蛋白复合物。然后,该复合物被路由到 mRNA 降解机制,导致 LHR mRNA 水平降低和黄体生成素受体的细胞表面表达减少。介绍了导致这些结论的研究。