The research plan is designed to determine the molecular mechanisms responsible for desensitization of the hormonally-responsive adenylyl cyclase system in the rabbit corpus luteum. This will be accomplished by analyzing the components of luteal adenylyl cyclase upon desensitization to human chorionic gonadotropin (hCG) and catecholamines. The components to be analyzed are the catalytic component, the stimulatory and inhibitory guanine nucleotide binding regulatory components, and receptors for gonadotropins and catecholamines. Through the use of enzyme assays, receptor-binding assays, reconstitution assays, gel electrophoresis, receptor photoaffinity labels and affinity chromatography, the reactions for inducing the desensitized state will be established. Furthermore, we will test the hypothesis that a phosphorylation event is associated with desensitization and determine which components of the luteal adenylyl cyclase system are phosphorylated. Results will shed new light into the mechanisms involved in the regulation of corpus luteum function and should help in the development of contraceptives designed to alter luteal function in early pregnancy or chemotherapeutic agents for gonadal cancers.
