Progesterone (P) facilitates the expression of sexually receptive behaviors in non-primate female mammals and has been implicated in the etiology of cyclical mood changes in humans (premenstrual syndrome). The mechanisms through which P and its primary metabolite, 5Alpha-dihydroprogesterone (DHP), affect neural tissues and behavior, however, have not yet been completely described. Because receptor binding is recognized as a critical first step in the production of steroid-mediated effects, the goal of the proposed research will be to examine the interaction of P and DHP with cellular progestin receptors (PR) in the brain. This will be accomplished by developing an assay for neural PR in which 3H-P and 3H-DHP can be used as ligands, a procedure which is currently unavailable. The assay will then be used to compare P and DHP binding in two strains of mice (CD-1, Swiss-Websster) that are differentially sensitive to the behavioral effects of P and DHP. Since CD-1 females respond to both progestins while SW females are insensitive to DHP, the strain comparison should provide a powerful tool for characterizing a possible molecular basis for sensitivity (or insensitivity) to P and DHP as well as providing information about the induction of these receptors. The results should therefore provide insights into a major neuroendocrine process involved in cyclical behavioral changes in females and may also help generate new hypotheses concerning the possible role of progestins in premenstrual syndrome.
