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We have recently reported that the adenylate cyclase activator, forskolin, induces in the rat ovarian follicle both cAMP accumulation and oocyte maturation. We demonstrate here, on the other hand, that the spontaneous maturation in vitro of isolated rat cumulus-enclosed oocytes is inhibited by forskolin. The inhibitory effect of forskolin is dose dependent with an ED50 at 15 microM. Forskolin inhibition decreases gradually with time, being completely relieved by 20 h of culture. Methylisobutylxanthine significantly prolongs the duration of the inhibitory action of forskolin. In addition to its inhibitory effect on oocyte maturation, forskolin triggers the cumulus-oocyte complex to generate cAMP. Cyclic AMP accumulation is maximally stimulated by 100 microM of forskolin with an ED50 at 60 microM. The potency of the cumulus-oocyte complex to respond to forskolin in terms of cAMP accumulation decreases with time. The pattern of the decrease in the potency of the cumulus-oocyte complexes to generate cAMP corresponds with the relief of its inhibitory influence on the oocyte. These results indicate that inhibition of maturation of the cumulus-enclosed oocyte may be coupled to elevation of cAMP levels in the cumulus-oocyte complex. As isolated cumulus-free oocytes are not inhibited by forskolin, we suggest that in the cumulus-enclosed oocyte system, cAMP generated by the cumulus cells is apparently transferred to the oocyte and maintains it in a meiotically arrested state. Maturation in this system occurs upon relief of inhibition which results from cessation of cAMP generation by the cumulus cells.

Spontaneous Maturation In Vitro of Cumulus-Enclosed Rat Oocytes Is Inhibited by Forskolin