Since androgens are known to be essential for the completion of spermatogenesis, it is of considerable interest to understand the influences of androgens on testicular cells in molecular terms. Since the Sertoli cells of the seminiferous tubule are thought to play a role in the control of spermatogenic process and we have shown that these cells have androgen receptors, the primary effort of this work will be directed toward defining in biochemical terms androgen-dependent functions of the Sertoli cell and attempting to look at these parameters in the setting of the seminiferous tubule. This proposal also seeks to extend earlier findings on androgen receptor dynamics by using an immunological probe of receptor levels. We will study the effect of androgens on maturational aspects of Sertoli cell function during the first wave of spermatogenesis, including the measurment of newly synthesized cellular and secreted proteins, as detected by 2-dimensional electrophoresis, identified Sertoli cell secretory products or functions, androgen receptor levels, total and poly A+ RNA profiles, translated protein patterns and RNA hybridization to selected cDAN probes. We will attempt to correlate androgen receptor dynamics temporally and quantitatively with selected responses elicited by androgens and to study the effect of other hormones and factors on the responsiveness of the Sertoli cell to androgens. We propose to compare biochemical events accompanying seminiferous tubular development In Vitro with comparable patterns in Sertoli, peritubular and germ cells of corresponding maturity and assess the effect of androgens on these events. We also propose to generate monoclonal antibodies to Sertoli cell androgen receptor for the study of receptor dynamics in the Sertoli cell.
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