FSH RECEPTOR--STRUCTURE AND FUNCTION

卵泡刺激素受体(FSH-R)，存在于睾丸支持细胞等 卵巢颗粒细胞，结合循环FSH和转导结合 激活Gs蛋白。从生理上讲， 这些靶细胞对循环中的FSH是至关重要的 男性的精子发生和女性的卵泡发育。 从大鼠FSH-R基因的克隆中，现在已经知道这是一种 受体是由一个大的N-末端组成的单一多肽 胞外结构域(它包含三个潜在的N-连接的位点 糖基化)连接到与其他G同源的C-末端的一半 蛋白偶联受体(因此可能跨越质膜 七次)。因此，FSH-R的整体结构组织是 与在促黄体生成素/促性腺激素和促甲状腺激素受体上观察到的类似。把这些放在一起 三种糖蛋白激素受体似乎组成了一个独特的亚群。 在G蛋白偶联受体家族中，它们含有大量的 胞外结构域。 重要的是，FSH-R基因的克隆现在可以让研究人员 追问与结构和机制有关的更详细的问题 这种受体的作用。具体地说，我们提出的具体目标是 以下内容：(1)表达编码胞外域的基因 哺乳动物细胞中的FSH-R。鉴定被截断的受体并验证 该区域赋予高亲和力结合和结合特异性。(2) 确定细胞外域糖基化的作用 FSH-R(3)建立FSH-R过表达系统，建立FSH-R过表达系统 FSH-R的胞外区，并对其进行特性分析 表达。(4)测定与激素结合有关的氨基酸和 受体-Gs蛋白的偶联和激活。 尽管仅这些研究的结果就会提供新的信息 关于FSH-R，他们也将为更多 在未来的详细研究中。还预计基本的 从这些研究中学到的知识将对理解 或许还能控制生育和不孕。

The FSH receptor (FSH-R), present on testicular Sertoli cells and on ovarian granulosa cells, binds circulating FSH and transduces that binding into the activation of a Gs protein. Physiologically, the response of these target cells to circulating FSH is critical for normal spermatogenesis in the male and for follicular development in the female. From the cloning of the cDNA for the rat FSH-R, it is now known that this receptor is a single polypepeptide which consists of a large N-terminal extracellular domain (which contains three sites for potential N-linked glycosylation) attached to a C-terminal half which is homologous to other G protein-coupled receptors (and thus presumably spans the plasma membrane seven times). Thus, the overall structural organization of the FSH-R is similar to that observed in the LH/CG and TSH receptors. Together these three glycoprotein hormone receptors appear to comprise a unique subgroup within the family of G protein-coupled receptors in that they contain large extracellular domains. Importantly, the cloning of the cDNA for the FSH-R now allows investigators to pursue more detailed questions pertaining to the structure and mechanism of action of this receptor. Specifically, the specific aims we propose are the following: (1) Express a cDNA encoding the extracellular domain of the FSH-R in mammalian cells. Characterize the truncated receptor and verify that this region confers high affinity binding and binding specificity. (2) Determine the role of glycosylation of the extracellular domain of the FSH-R. (3) Establish a system for the overexpression of FSH-R and the extracellular domain of the FSH-R and characterize the proteins thus expressed. (4) Determine those amino acids involved in hormone binding and receptor-Gs protein coupling and activation. Although the results of these studies alone will provide novel information concerning the FSH-R, they will also provide the groundwork for more detailed studies in the future. It is also anticipated that the basic knowledge learned from these studies will be valuable towards understanding and perhaps controlling fertility and infertility.