description) The long-term research objectives of the investigator are to determine the molecular mechanisms that regulate the expression of Mullerian Inhibiting Substance (MIS) and how MIS signals Mullerian duct regression during mammalian reproductive tract development. With the investigator's recent finding that a major regulator of MIS gene expression in the developing male gonad is the orphan nuclear receptor, steroidogenic factor-l (SF-1) and preliminary identification of a soluble protein factor secreted by the Sertoli cell referred to as Gonadal Activation Factor (GAF) that activates SF-1, the following specific aims are proposed: 1) to complete the characterization of the MIS promoter in vivo; 2) to purify, characterize and clone GAF; and 3) to characterize the mechanism of GAF activation of SF-1. These studies will provide insight into the molecular mechanisms that govern mammalian sex determination and reproductive development and the basis of human sexual disorders.
