Does the guanine nucleotide regulatory protein Ni mediate progesterone inhibition of Xenopus oocyte adenylate cyclase?

Abstract

In Xenopus laevis oocytes progesterone is able to inhibit directly the plasma membrane adenylate cyclase activity and induce reinitiation of meiotic maturation. To determine whether progesterone inhibition is mediated by the inhibitory guanine nucleotide‐binding regulatory component of adenylate cyclase, Ni, the effect of the Bordetella pertussis toxin (IAP) and limited proteolysis on progesterone action in oocytes was investigated. Treatment of oocyte membranes with islet activating protein (IAP) in the presence of [32P]NAD led to incorporation of radiolabel into a 41 000‐dalton membrane protein. However, exposure of isolated oocytes to 100 ng/ml IAP for up to 24 h, or oocyte membranes with concentrations of toxin as high as 100 micrograms/ml, had no effect on either progesterone inhibition of adenylate cyclase or induction of maturation. Similarly, limited alpha‐chymotrypsin proteolysis of oocyte membranes failed to modify progesterone‐induced inhibition of adenylate cyclase. In contrast, inhibition of human platelet adenylate cyclase by epinephrine, acting via a GTP‐dependent, alpha 2‐adrenergic receptor‐mediated pathway, is almost completely abolished by both IAP treatment and limited proteolysis of platelet membranes. These data indicate that unlike attenuation of platelet enzyme activity, the inhibition of adenylate cyclase in oocyte membranes by progesterone does not occur via a classical Ni‐mediated pathway.

xRic‐8 is a GEF for Gsα and participates in maintaining meiotic arrest in Xenopus laevis oocytes

“…The non-genomic mechanism, through which progesterone triggers meiosis resumption, is not completely understood, however it is well established that at a very early step of the process, which takes place at the plasma membrane, inhibition of the enzyme AC occurs (Maller et al, 1979;Bravo et al, 1978;Schorderet-Slatkine et al, 1978;Jordana et al, 1984). Progesterone induced AC inhibition has been shown to be GTP dependent and requires the participation of a Pertussis toxin insensitive G-protein (Jordana et al, 1981a(Jordana et al, ,b, 1984Goodhardt et al, 1984;Olate et al, 1984;Sadler et al, 1984;Olate et al, 1985). In addition, AC activity stimulated by positive G-protein modulators such as Gpp(NH)p, GTPgS, aluminum fluoride and Cholera toxin, is inhibited by progesterone, pointing out to the participation of a Gsa type of G-protein (Jordana et al, 1981a(Jordana et al, , 1984Sadler and Maller, 1981).…”

A Gβγ stimulated adenylyl cyclase is involved in xenopus laevis oocyte maturation

“…Progesterone, through an unknown non genomic mechanism, triggers the maturation process Godeau et al, 1978;Masui and Clarke, 1979), which involves reduction of oocyte cAMP levels through adenylyl cyclase (AC) inhibition (Maller and Krebs, 1977;Bravo et al, 1978;Maller et al, 1978;Schorderet-Slatkine et al, 1978SchorderetSlatkine and Baulieu, 1982;Jordana et al, 1984). Progesterone induced AC inhibition has been shown to be GTP-dependent, and requires the participation of a Pertussis toxin insensitive G-protein (Jordana et al, 1981a(Jordana et al, ,b, 1984Sadler and Maller, 1981;Goodhardt et al, 1984;Olate et al, 1984Olate et al, , 1985Sadler et al, 1984). Activation of AC by different G-protein stimulators such as Gpp(NH)p, GTPgS, aluminum fluoride, and Cholera toxin, is inhibited by progesterone, indicating the participation of Gas in steroid action (Jordana et al, 1981a(Jordana et al, , 1984Sadler and Maller, 1981;Antonelli et al, 1986;Gallo et al, 1995).…”

Antibodies to the ras gene product inhibit adenylate cyclase and accelerate progesterone-induced cell division in Xenopus laevis oocytes.

“…Recently, it has been demonstrated that the yeast homolog of p21 has direct effects upon intracellular levels of cyclic AMP and that GTP-dependent adenylate cyclase activity in yeast cells requires a normal ras genotype (27) otide exchange (16,17,18). However, in contrast to hormonal inhibition of adenylate cyclase in other cell systems, inhibition of oocyte adenylate cyclase by progesterone is not mediated via the inhibitory guanine-nucleotide-binding subunit, G1, in the conventional manner (7,14,19). To determine whether p21 might be involved in the regulation of oocyte cell division, antibodies to p21 were microinjected into oocytes, and subsequent changes in the time course of progesterone-induced GVBD were monitored.…”