STRUCTURAL STUDIES OF RECEPTORS FOR LACTOGENIC HORMONES

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During pregnancy, the lactogenic hormones prolactin and placental lactogen participate in the regulation of processes such as mammary gland differentiation, steroidogenesis, somatic growth and intermediary metabolism in a variety of animals. Regulation of these processes is achieved through fluctuations in the levels of the lactogenic hormones. We know that lactogenic hormones are structurally similar and possess overlapping biological activities, but very little is known about their receptors. It is not known whether these hormones send a biochemical signal through a receptor unique to each hormone or, alternatively, whether they function through a common receptor. Since the lactogenic hormones influence a variety of biological processes, it is important to have knowledge about receptors for each specific lactogen over the course of pregnancy. The mouse will be used as a biological model to study lactogenic receptors over the course of gestation. A prolactin receptor will be isolated from mouse mammary glands. The purified receptor will be structurally analyzed by peptide mapping, amino acid analysis, N-terminal analysis, and other biochemical means. An antiserum will be generated with purified prolactin receptor and employed as an immunochemical probe. After crosslinking radiolabelled lactogens to receptors from organs removed on different days of gestation, hormone- receptor complexes will be analyzed by two-dimensional polyacrylamide gel electrophoresis, immunoblotting and autoradiography for determination of the multiplicity of lactogenic receptors. Electroimmunochemical techniques will be used to ascertain structural similarities that exist among prolactin receptors of different target organs. Ontogeny of lactogenic receptors during pregnancy in both the mother and fetus will be monitored by electrophoresis and immunostaining of receptors from several tissues. The potency and specificity of the interaction of glycosylated prolactin with receptors will be examined using radioreceptorassays, crosslinking and immunochemical methodologies. These studies should provide information that will improve our understanding about receptors for lactogenic hormones in the mouse, and perhaps will lead to an understanding about receptors for human lactogenic hormones.