Oocyte maturation is regulated by modulation of the action of FSH in cumulus cells.

A biochemical and cellular model is described for the regulation of oocyte maturation by modulation of FSH-dependent accumulation of cyclic AMP (cAMP) in the rat oocyte-cumulus complex (OCC). We propose that accumulation of cAMP in cumulus cells is specifically stimulated by FSH and modulation of this response to FSH is a primary site for the control of oocyte maturation. On the one hand, adenosine amplifies inhibition of oocyte maturation by up-modulation of FSH-sensitive accumulation of cAMP. In contrast, calcium ionophores induce oocyte maturation by down-modulation of FSH-dependent accumulation of cAMP. We suggest that adenosine and calcium interact at a similar site because adenosine reverses the calcium-dependent inhibition of the action of FSH. This model appears to have physiological relevance since induction of oocyte maturation by gonadotropin in the intact follicle occurs in parallel with inhibition of the FSH-sensitive accumulation of cAMP in the OCC. Moreover, gonadotropin-induced desensitization of the OCC to the action of FSH appears to precede the loss of intercellular junctional processes, as measured indirectly by uptake of radiolabelled uridine into the oocyte. Thus, a decrease in the FSH-sensitive accumulation of cAMP in cumulus cells, produced either by direct elevation of the intracellular concentration of calcium or by treatment of the intact follicle with gonadotropin, results in oocyte maturation. On the other hand, an increase in the cAMP response to FSH, produced by agents such as adenosine, results in inhibition of oocyte maturation. Thus, responsiveness of the cumulus cells to FSH appears to be acutely modulated and this site may be a major determinant for the regulation of oocyte maturation.