Our proposed studies are directed at obtaining a detailed understanding of the mechanism of action of a hypothalamic hormone, thyrotropin-releasing hormone (TRH). The studies will examine several aspects of TRH action utilizing clonal, responsive pituitary cell lines (GH cells). We will extend studies which have demonstrated that TRH: 1) activates a distinctive pathway of protein phosphorylation which involves neither cyclic AMP nor Ca2 ion influx; 2) rapidly promotes 45Ca efflux from perifused, prelabeled GH cells; 3) rapidly stimulates phosphoplipid metabolism in a receptor-mediated manner. The ultimate goal of the proposed studies is to identify post-receptor events involved in initiating biological responses to TRH (s.a. increased prolactin release from GH cells). GH cell variants altered in cyclic AMP or Ca2 ion actions have been isolated and characterized. Availability of clonal variants should aid in defining cellular pathways of TRH action.
