Inhibition of the adenylyl cyclase and activation of the phosphatidylinositol pathway in oocytes through expression of serotonin receptors does not induce oocyte maturation

Abstract

The identification of the initial signaling events induced by progesterone in Xenopus oocyte maturation was approached by expressing serotonin receptors and by using pharmacological agents. Suppression of phospholipase C (PLC) activity in oocytes by U-73122 or stimulation of oocyte adenylyl cyclase (ACase) by forskolin inhibited progesterone-induced reinitiation of meiotic cell division. Microinjection of cAMP-dependent protein kinase (PKA) pseudosubstrate, PKI, into oocytes--or pretreatment of oocytes with PKA inhibitor, H-89--did not induce oocyte maturation, but both treatments potentiated the rate of progesterone-induced germinal vesicle breakdown (GVBD). In addition, reduced PKA activity by H-89 reversed the inhibition of GVBD caused by U-73122. Expression and activation of the serotonin receptor type 1a or type 2c lowered intracellular cAMP level or mobilized Ins(1,4,5)P3, respectively. These oocytes, however, did not undergo maturation upon serotonin stimulation. Co-expression of these receptors also did not trigger maturation, but it significantly accelerated the rate of GVBD induced by progesterone. From these data, we conclude that (1) changes in levels of these second messengers may well be coupled with progesterone signaling; (2) an initial decrease in cAMP and production of Ins(1,4,5)P3/DG may not be absolute requisites for progesterone-induced meiotic maturation: (3) cross-talk mechanisms between adenylyl cyclase and phosphoinositide signal transduction pathways may exist in the process of progesterone-induced reinitiation of meiotic cell cycle.