INTRATESTICULAR REGULATION OF LEYDIG CELL FUNCTION

睾丸间质细胞功能的调节

• 批准号: 2194572
• 负责人: Vassilios Papadopoulos
• 金额: $ 6.75万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2194572
• 关键词: Leydig cells; Sertoli cells; affinity chromatography; binding proteins; cell cell interaction; cell cycle; cell growth regulation; diazepam; gene expression; hormone regulation /control mechanism; immunologic assay /test; laboratory mouse; laboratory rabbit; laboratory rat; luteinizing hormone; molecular cloning; monoclonal antibody; protein purification; protein sequence; protein structure function; receptor binding; secretory protein; spermatogenesis; steroid biosynthesis; tissue /cell culture

A prerequisite for normal spermatogenesis is the coordination of Leydig cell function with the needs of the spermatogenic phase of the seminiferous epithelium. This is achieved through the actio of gonadotropins, and a reciprocal transfer of information between Leydig cells and Sertoli cells. It is also now clear that a local modulation of Leydig and Sertoli cells, possibly independent of LH and FSH, occurs within the testis and that these paracrine interactions are important in regulating sperm production under normal conditions, or as part of a local compensatory mechanism which operates when Leydig cell function needs to be supported. The proposed studies focus on the regulation of Leydig cell function by Sertoli cells. Our first specific aim is the purification and characterization of the Sertoli cell secreted protein which stimulus Leydig cell steroidogenesis. Generation of antibodies, partial amino acid sequencing, and molecular cloning of the bioactive protein will permit us to determine its structure/function relationship[ as well as its relationship to other known protein(s). Identification of the receptor system through which this Sertoli cell protein acts on Leydig cells, and of the step(s) in the steroid biosynthetic pathway which are regulated by this protein is our second specific aim. Part of these studies will be to determine whether and how this protein modulates Leydig cell responsiveness to LH. In view of our recent findings that the polypeptide diazepam binding inhibitor (DB or endozephine) is a paracrine/autocrine regulator of Leydig cell proliferation and steroidogenesis, our third specific aim focuses on the understudying of the mechanism of action of DB on Leydig cells.

正常精子发生的先决条件是Leydig的协调 细胞功能，满足了精子阶段的需求 生精上皮。 这是通过 促性腺激素和Leydig之间信息的相互传递 细胞和Sertoli细胞。 现在也很清楚，本地调制 可能独立于LH和FSH的Leydig和Sertoli细胞的出现 在睾丸中，这些旁分泌相互作用在 调节正常条件下的精子产生，或 Leydig细胞功能时运行的局部补偿机制 需要支持。 拟议的研究重点是调节 Sertoli细胞的Leydig细胞功能。 我们的第一个具体目标是 Sertoli细胞分泌蛋白的纯化和表征 哪些刺激leydig细胞类固醇生成。 产生抗体， 部分氨基酸测序和生物活性的分子克隆 蛋白质将使我们能够确定其结构/功能关系[ 以及其与其他已知蛋白质的关系。 鉴别 这种Sertoli细胞蛋白通过的受体系统的作用 leydig细胞和类固醇生物合成途径中的步骤 由该蛋白质调节的是我们的第二个特定目标。 一部分 这些研究将是确定该蛋白是否调节的以及如何调节 Leydig细胞对LH的反应。鉴于我们最近的发现是 多肽地西爱结合抑制剂（db或eshosephine）是一个 Leydig细胞增殖的旁分泌/自分泌调节剂 类固醇生成，我们的第三个特定目的侧重于研究 DB对Leydig细胞的作用机理。