Activin plays a critical role in the regulation of the pituitary-gonadal axis. The long-term objectives of the proposed research are to better understand the role of activin in the regulation of pituitary cell physiology. The short-term goals are to establish the basis for this understanding by answering some specific questions concerning the mechanisms underlying activin signal transduction. Preliminary data from our laboratory demonstrates Smad7 expression in the anterior pituitary. While it is clear that Smad7 is an antagonist of activin signaling, its role in the pituitary remains largely unexplored. We hypothesize that Smad7 is an important modulatory factor within the pituitary, inhibiting activin-regulated pituitary cell function. In Specific Aim I, studies will examine the production and regulation of Smad7 expression in rat anterior pituitary cells, in vitro. In Specific Aim II, studies aim to characterize the structure of the mouse Smad7 gene and its regulation by activin in a gonadotrope cell line. Lastly, under Specific Aim III, we propose to examine the role of Smad7 on basal and activin-regulated gonadotrope cell function. The studies outlined in the present research proposal are important as defining the activin signaling pathway is a pivitol step toward better understanding the endocrine role of activin, the pathogenesis of various endocrine disorders, and the development of tools toward the treatment of pituitary dysfunction.