Myometrial adenylyl cyclase protein decreases on the last day of pregnancyin the rat

To determine whether gestation-related changes in responsiveness of the rat uterus to beta-adrenergic agonists are mediated at the level of adenylyl c yclase, we measured myometrial adenylyl cyclase activity and protein quanti ties during pregnancy and labor, In rat myometrial membranes, basal adenyly l cyclase activity increased from the nonpregnant state to mid (Days 12-14) and then late (Days 18-20) gestation and then decreased intrapartum (Day 2 2). Stimulated adenylyl cyclase activity, at the level of the beta-adrenerg ic receptor (isoproterenol, 10(-4) M), the G protein (GTP, 10(-5) M), or th e adenylyl cyclase enzyme (MnCl2r 20 mM), was similarly altered during gest ation. Total adenylyl cyclase protein was quantified by [H-3]forskolin bind ing assay in myometrial membranes from nonpregnant and pregnant (Day 14, Da y 20, Day 21, and intrapartum Day 22) rats. Adenylyl cyclase protein increa sed progressively from nonpregnant rats to pregnant rats at mid (Day 14) an d late (Day 20) gestation, but it decreased abruptly to nonpregnant Levels on Day 21, the day before parturition, and remained at similar levels on Da y 22 (intrapartum). The gestation-related increase in expression of myometr ial adenylyl cyclase protein may facilitate uterine quiescence during pregn ancy, and the abrupt decrease of adenylyl cyclase protein on the last day o f pregnancy may be a contributing mechanism for the initiation of labor.