Adenylate cyclase in Xenopus laevis oocytes: characterization of the progesterone-sensitive, membrane-bound form.

Progesterone-induced reinitiation of meiosis in Xenopus laevis oocytes involves a decrease in cAMP level. In these cells, adenylate cyclase is compartmentalized, with 25-30% in the plasma membrane fraction P-10000 (sedimenting at 10000 X g) and greater than 50% in the cytosol. Soluble adenylate cyclase appears not to be regulated via a GTP-binding regulatory protein (G/F) and is insensitive to progesterone. In contrast, membrane-bound adenylate cyclase seems to be linked to G/F, since it is stimulated by sodium fluoride, guanyl-5'-imidodiphosphate (Gpp(NH)p) and by cholera toxin; it is also inhibited by progesterone. The steroid inhibition is displayed towards basal and stimulated activities. The extent of progesterone inhibition of basal activity is dependent on Mg2+ and Mn2+ concentrations. The hormonal effect is independent of GTP concentration and is observed even in the presence of the non-hydrolysable analogue of GTP, Gpp(NH)p. The progesterone effect is not mediated by adenosine. Exposure of the P-10000 fraction to 5'-deoxy-5'-S-isobutylthioadenosine (a methyltransferase inhibitor) increases adenylate cyclase activity.