The objectives of the proposed research are (a) to examine in detail several aspects of uterine progestatational metabolism in the rat which may be related to the process of nidation and uterine decidual sensitivity, and (b) to determine the roles of estrogen and progesterone in these metabolic parameters. Based on previous work, a model of progestational differentiation in the uterus of the rat suggested that significant alterations in pyridine nucleotide metabolism should occur transiently in the endometrium at the time of decidual sensitivity. Preliminary data indicate that in fact significant alterations in NADP are uniquely measured during this period of progestation. To examine this phenomenon in depth, measures will be made of NAD, NADH, NADP, NADPH, NAD-kinase and NAD-glycohydrolase activities in endometrium. The effects of estrogen, progesterone and the physiologic combination of steroids on the quality and timing of the response will be evaluated. To study how a relatively nonspecific stimulus may be transduced into a deciduogenic response, measures will be made of the membrane-based adenylate cyclase system and its hormonal control (adenylate cyclase, cAMP and phosphodiesterase activity). Preliminary data reveal a transient and unique shift in the cyclase activity on the 4th day of progestation, the time of maximal sensitivity to decidualization. The relationship of this pattern to the timed induction of the decidual response will be examined.