Cyclic AMP-Mediated Control of Meiosis: Effects of Progesterone, Cholera Toxin, and Membrane-Active Drugs in Xenopus laevis Oocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS 1982-02, Vol.79 (3), p.850-854
• Main Authors: Schorderet-Slatkine, Sabine, Schorderet, Michel, Baulieu, Etienne-Emile
• Format: Article
• Language: English
• Subjects: Animals; Cell division; Cholera; Cholera Toxin - antagonists & inhibitors; Cholera Toxin - pharmacology; Cyclic AMP - physiology; Developmental biology; Dosage; Female; Gallopamil - pharmacology; Hormones; Insulin; Meiosis; Meiosis - drug effects; Mersalyl - pharmacology; Oocytes; Oocytes - physiology; Ovum - physiology; Phosphatidylinositols - antagonists & inhibitors; Phosphodiesterase Inhibitors - pharmacology; Progesterone - pharmacology; Propranolol - pharmacology; Steroids; Toxins; Xenopus laevis; Zinc - pharmacology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.79.3.850

Progesterone depressed rapidly (50% at 1 min) and persistently cyclic AMP (cAMP) concentration that had been elevated by cholera toxin in Xenopus laevis oocytes. cAMP remained below 1 pmol per oocyte (mean basal level) for ≈ 1 hr and thereafter rose to ≈ 120% of control values, while germinal vesicle (nucleus) breakdown did not occur. In the absence of cholera toxin, progesterone treatment for 6 hr maintained cAMP concentration below the basal level (but not lower than 80%), and germinal vesicle breakdown occurred. Experiments in the presence of phosphodiesterase inhibitors suggested that progesterone modulates adenylate cyclase activity. The maturation promoting factor, which is formed after 3-5 hr of progesterone treatment and provokes germinal vesicle breakdown after its injection into untreated oocytes, also decreased cAMP concentration, an observation that may explain its ``autoamplification.'' Nonsteroidal inducers of meiosis reinitiation (e.g., propranolol, methoxyverapamil, mersalyl) diminished the cholera toxin-mediated accumulation of cAMP, in contrast to compounds devoid of meiotic-inducing capacity and antagonists to progesterone action, such as gammexane (an inositol analogue) and 5′-deoxy-S-(2-methylpropyl)-5′-thioadenosine (a methylase inhibitor), that increased the nucleotide level. The fine control, suggested by the effects of small changes in cAMP levels, gives evidence of great sensitivity to a critical determinant governing meiotic cell division.