Steroid hormones regulate differentiation, growth, and developmental maturation of most tissues. Progesterone is a steroid hormone that influences numerous biological functions, including reproduction. Because of its critical requirement in the initiation and maintenance of pregnancy, understanding its mode of action is important to investigators in reproductive endocrinology. Many tissues (breast, endometrium) which normally depend on progesterone for their functions continue to be influenced by the steroid after their transformation to a malignant state. The growth of some of these abnormal tissues can be arrested by endocrine therapy. Although the precise mechanism of progesterone action is not well understood, biological actions of progesterone are mediated by progesterone receptors (PR). One approach to understanding the function of PR is to examine its regulation by post-translational modification via phosphorylation. The long-term goal of this project is to develop a model system to study the regulation of chicken oviduct progesterone receptor (cPR) by phosphorylation. Phosphorylation of cPR will be examined and compared under physiological and cell-free conditions. The extent of phosphorylation of cPR, and the nature and location of phosphorylated sites will be determined by methods that include SDS-PAGE, autoradiography and peptide mapping. A major emphasis also will be to identify the physiological protein kinase(s) responsible for phosphorylation of cPR. Preliminary work performed under this project has revealed the presence of a hormone specific, temperature-sensitive kinase that copurified with cPR and appears to be a good candidate for a biological modifier of progesterone action. The results of the proposed studies should lead to a better understanding of the regulation of steroid hormone action.
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