The P-50 Specialized Population Research Center described in this proposal is composed of seven research projects that are designed to achieve a broad understanding of the testis and its two major products, spermatozoa and testosterone. The studies of fetal gonads will define serum factors responsible for testicular differentiation and their mechanisms of action. The function of Sertoli cells will be investigated using assays for well-studied testicular markers, such as androgen binding protein and transferrin, in concert with newly identified products that are dependent both on hormones and the stage of the seminiferous tubular epithelium. The factors that are responsible for Sertoli cell growth, secretion and self-assembly into tubular structures will be investigated using clonal cell lines, primary cultures and isolated segments of the seminiferous tubule. Studies on the mechanism of androgen action in mouse kidney will provide insight into the structure and function of the androgen receptor, and will define the mechanism of activation of rapidly and slowly responding androgen sensitive genes. The maturation of spermatozoa in the female reproductive tract will be examined in order to understand how structural changes relate to the increased motility that is acquired once the sperm have left the epididymis. Finally, the technology developed throughout the Center will be applied to men in order to understand the etiology of infertility, a condition(s) which affects a large portion of the population.
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