GONADAL RECEPTORS/MECHANISMS OF ACTION OF PEPTIDE HORMONES IN STEROIDOGENIC CELLS

1)促黄体激素受体是一个七跨膜的G 具有高亲和力激素结合位点的蛋白质偶联受体 位于其N端胞外区。突变研究已经 确定了两类特定的胞外半胱氨酸残基 是表面表达或激素结合所必需的。四个都是 外显子1中的非保守半胱氨酸是结合活性所必需的 而外显子5和6(109,134)中保守的半胱氨酸对 荷尔蒙结合。外显子1半胱氨酸之间以及外显子1之间的二硫键 这些研究表明，外显子5和外显子6的基因是相同的。除了两个之外，所有的 剩余的8个半胱氨酸，包括环1和环2(外显子)中的半胱氨酸 7-11)产生了受体转位到细胞表面的缺陷，但 不是荷尔蒙结合的。因此，外显子1对半胱氨酸的需求 激素结合活性与新生细胞的加工无关 受体。与N-氨基葡萄糖结合的第一外显子半胱氨酸 需要Asn152和Asn173上的糖链残基 变性/还原成熟蛋白激素结合域的重折叠 受体的活性构型。糖类残留物是 成熟蛋白活性构象的稳定/获得 受体和新生受体。2)隔震和结构 促肾上腺皮质激素释放激素基因的特征包括 其内含子/外显子组织的完整图谱和 垂体腺剪接变异体和新剪接变异体的分离 间质细胞CRF受体。这些研究表明， 垂体和间质细胞之间信号转导的差异是 不能归因于不同受体亚型的表达。他们 也为无内含子之间的进化联系提供了证据 糖蛋白受体的跨膜/胞浆模块和 CRF受体的含有内含子的模块。3)拆解建筑群 催乳素受体基因的结构已经确定了启动子区域 和参与转录激活的调控元件 组织特异性启动子(PI-PIII)。启动子在乳腺中的应用 腺体已被确认。4)雄激素的关键酶--细胞色素P17 途径，被发现在其物种和组织特异性的差异 调控序列。氨基酸结构域中的这种差异 种内和种间羟基酶活性所需 (人/牛与鼠)的差异调节是一致的 类固醇生成细胞中裂解酶的活性。

1) The luteinizing hormone receptor is a seven transmembrane G protein-coupled receptor with a high-affinity hormone binding site located on its N-terminal extracellular domain. Mutational studies have identified two specific classes of extracellular cysteine residues that are required for surface expression or hormone binding. All four non-conserved cysteines from exon 1 are essential for binding activity and the conserved cysteines in exon 5 and 6 (109,134) are important for hormone binding. Disulfide bonding among cysteines in exon 1, and between those of exon 5 and 6, were indicated by these studies. All but two of the eight remaining cysteines, including those in loops 1 and 2 (exons 7-11) produced defects in receptor translocation to the cell surface but not in hormone binding. Thus, the requirement of cysteine in exon 1 for hormone binding activity is not related to processing of the nascent receptor. The exon 1 cysteines, in conjuction with the N-glucosamine residue of the glycosyl chains at Asn152 and Asn173, are required for refolding of the hormone binding domain of the denatured/reduced mature receptor to its active configuration. The sugar residues are required for stabilization/acquisition of the active conformation of the mature receptor and of the nascent receptor. 2) Isolation and structural characterization of the corticotropin-releasing hormone gene included the complete mapping of its intron/exon organization and the basis of the pituitary splice variants, and the isolation of novel spliced variants of the Leydig cell CRF receptor. These studies suggest that the differences in signal transduction between pituitary and Leydig cells are not attributable to the expression of different receptor isoforms. They also provide evidence for an evolutionary link between the intronless transmembrane/ cytoplasmic module of the glycoprotein receptors and the intron-containing module of the CRF receptor. 3) Unravelling the complex structure of the prolactin receptor gene has identified promoter regions and regulatory elements involved in transcriptional activation of the tissue-specific promoters (PI-PIII). The promoter utilized in the mammary gland has been identified. 4) CYP17, the key enzyme of the androgen pathway, was found to have species and tissue-specific differences in its regulatory sequences. Such differences in the amino acid domains required for hydroxylase activity within and between species (human/bovine vs. rat) are consistent with their differential regulation of lyase activity in steroidogenic cells.