HORMONAL REGULATION OF GENE EXPRESSION IN SERTOLI CELLS

支持细胞基因表达的激素调节

• 批准号: 2025141
• 负责人: DAVID R JOSEPH
• 金额: $ 26.73万
• 依托单位: APPLIED GENETICS LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2025141
• 关键词: Sertoli cells; androgen binding protein; complementary DNA; epididymis; gene expression; genetic regulation; genetic regulatory element; genetically modified animals; hormone regulation /control mechanism; laboratory mouse; laboratory rat; polymerase chain reaction; protein structure function; tissue /cell culture; transcription factor

Follicle-stimulating hormone (FSH) and androgens regulate Sertoli cell secretory proteins that function to control spermatogenesis. The expression of one of the Sertoli cell secretory proteins, androgen- binding protein (ABP), parallels the hormonal regulation of spermatogenesis. Because of this relationship, ABP has been widely used as a marker for Sertoli cell function. Although ABP is thought to be an extracellular androgen carrier protein, its function remains largely unknown. Previous studies in this laboratory on rat ABP have contributed to the overall knowledge of ABP gene regulation and ABP function. The results of these experiments have opened new routes for experimentation. This proposal outlines a plan to decipher the mechanisms of ABP gene regulation and to reveal the function of ABP in the testis and epididymis. This proposal has two specific aims: 1. Identify and characterize DNA regulatory elements and trans-acting factors that regulate the rat ABP gene. An emphasis will be placed on identifying the sequences and binding proteins that impart Sertoli cell specific expression. Whether the gene contains an active androgen regulatory element will also be determined. 2. Elucidate the functions of ABP in the testis and epididymis. These experiments will include characterization of a transgenic mouse line that overexpresses ABP and development of a mouse line that does not contain a functional ABP gene. Experiments to clone the cDNA that encodes the epididymal plasma membrane receptor are also proposed. The proposed studies will significantly increase our knowledge of ABP gene regulation and ABP function. This knowledge will expand our understanding of the role of the Sertoli cell in spermatogenesis and will aid in the identification of fertility defects and perhaps the development of new contraceptive techniques.

卵泡刺激素（FSH）和雄激素对支持细胞的调节 控制精子发生的分泌蛋白质类。 的 支持细胞分泌蛋白之一雄激素的表达， 结合蛋白（ABP），平行于激素调节， 精子发生由于这种关系，ABP得到了广泛的应用 作为支持细胞功能的标志。虽然ABP被认为是一个 细胞外雄激素载体蛋白，其功能主要保留 未知本实验室先前对大鼠ABP的研究有助于 ABP基因调控和ABP功能的全面知识。 的 这些试验成果，开辟了新的试验途径。 本研究提出了一个破解ABP基因作用机制的方案 研究ABP在睾丸中的作用， 附睾这项建议有两个具体目标： 1.识别和表征DNA调控元件和反式作用 调节大鼠ABP基因的因子。 重点将放在 鉴定赋予支持细胞的序列和结合蛋白， 具体表达。 基因中是否含有活性雄激素 还将确定监管要素。 2.阐明ABP在睾丸和附睾中的作用。这些 实验将包括表征转基因小鼠品系， 过表达ABP和开发不含 功能性ABP基因。实验克隆了编码 还提出了附睾质膜受体。 拟议的研究将大大增加我们对ABP的了解 基因调控和ABP功能。 这些知识将扩大我们的 了解支持细胞在精子发生和意志中的作用 有助于识别生育缺陷， 开发新的避孕技术。