MECHANISM OF ACTION OF PEPTIDE HORMONES IN STEROIDOGENIC CELLS

睾丸间质细胞对雄激素产生的控制受到直接调节， 促黄体生成激素通过特定的受体。 促性腺激素治疗 引起初始LH受体上调， 类固醇生成酶：“早期损伤”（在使用prengenolone之前）和“晚期损伤”（在使用prengenolone之前） 病变”E2依赖性（17 α-羟化酶17-20碳链酶）。 这些是 不依赖于受体丢失或蛋白激酶激活。 负 在未成熟或胎儿中未观察到受体和病变的控制 睾丸间质细胞 这个项目的目标是了解所涉及的步骤 睾丸功能的荷尔蒙控制。 我们已经证明 作为促性腺激素作用的结果，E2介导的脱敏是 由环状AMP依赖性芳香酶的早期激活启动， 其次是E2形成的显着上升，由于增加 底物可用性 Leydig细胞是E2合成的主要场所， 成年大鼠睾丸。 未成年大鼠芳香化酶活性较低 Leydig细胞可以解释在胎儿中观察到的脱敏缺乏 早期生活 在脱敏之前的E2作用包括增加 27 K E2调节蛋白的合成。 这种蛋白质被发现是 免疫学上类似于MCF-7的主要E2调节的27 K蛋白 细胞 这提供了用于检测E2作用的灵敏探针， 应证明对进一步功能和结构表征有用 蛋白质和E2在Leydig细胞核作用的研究 cell. 有一个连续的基础供应类固醇胆固醇， 不管促性腺激素的存在， 可能是由内源性类固醇的水平调节的。 早期病变的 不是由于前体的浓度不适当，因为 线粒体内膜中的胆固醇水平增加。 一 在线粒体中鉴定了热不稳定抑制蛋白因子， hCG处理后，其表达明显增加。 这个因素， 竞争性抑制胆固醇侧链裂解活性， 有助于早期类固醇损伤，也可能作为一个 类固醇激素生物合成的内源调节剂。

The control of androgen production by the Leydig cell is directly regulated by luteinizing hormone via specific receptors. Treatment with gonadotropin causes initial LH receptor up-regulation, and desensitization of steroidogenic enzymes: "early lesion" (prior to prengenolone) and "late lesion" E2-dependent (17 Alpha-hydroxylase 17-20 desmolase). These are independent of receptor loss or protein kinase activation. The negative control of receptors and lesions is not observed in the immature or fetal Leydig cell. The goal of this project is to understand the steps involved in the hormonal control of testicular function. We have demonstrated that as a result of gonadotropin action, E2-mediated desensitization is initiated by a cyclic AMP-dependent early activation of aromatase, which is followed by a significant rise in E2 formation due to an increased substrate availability. Leydig cells are the major site of E2 synthesis in theadult rat testis. The low aromatase activity observed in immature rat Leydig cells could explain the lack of desensitization observed in fetal and early life. E2 action that precedes desensitization includes increased synthesis of a 27K E2-regulated protein. This protein was found to be immunologically similar to a major E2-regulated 27K protein of MCF-7 cells. This provides a sensitive probe for detection of E2 action and should prove useful for further functional and structural characterization of the protein and for studies of the nuclear actions of E2 in the Leydig cell. There is a continous basal supply of steroidogenic cholesterol in the mitochondrion regardless of the presence of gonadotropins, a process probably regulated by the levels of endogenous steroids. The early lesion is not due to an inappropriate concentration of precursors, since the levels of cholesterol in the inner mitchondrial membrane are increased. A heat-labile inhibiting protein factor was identified in mitochondria and shown to be markedly increased by hCG treatment. This factor, which competitively inhibits cholesterol side-chain cleavage activity, could contribute to the early steroidogenic lesion and may also serve as an endogenous modulator of steroid hormone biosynthesis.