HORMONAL REGULATION OF GENE EXPRESSION IN SERTOLI CELLS

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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.