PRE-OVULATORY CHANGES IN RAT FOLLICULAR CYCLIC AMP AND SENSITIVITY TO GONADOTROPHINS

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Abstract
Stimulation of ovarian follicles by high concentrations of gonadotropins was reported to induce a refractory state in the follicles to further stimulation by the same agent. The present study was undertaken a determine whether a physiological gonadotropic stimulus would induce a similar desensitization. The levels of cyclic AMP (cAMP) were measured in rat pre-ovulatory follicles before and after the estimated period of gonadotropin release. The PMSG [pregnant mare''s serum gonadotropin] injected pre-pubertal rat was used as a model of spontaneous ovulation as previously described. Follicles were explanted before and after the period of gonadotropin release on the day before ovulation (day 30 in the present model) and cAMP was measured either directly or after 1-2 h of incubation. The follicles explanted in the evening of day 30 showed higher levels of cAMP than those isolated in the same morning irrespective of their being incubated or not. Follicular lactic acid production and progesterone synthesis as measured in the incubation medium showed the same pattern. The increase in all 3 parameters in evening follicles could be prevented by giving the animals pentobarbitone before the estimated gonadotropin release. When the follicles were extirpated in the evening of day 30 and incubated in the presence of LH [luteinizing hormone] or FSH [follicle stimulating hormone] significantly higher concentrations of the 2 hormones were needed to elicit a further increase in cAMP as compared to follicles isolated in the morning of the same day or from rats treated with pentobarbitone. The pre-ovulatory surge of gonadotropins induces a desensitization of the cAMP system of rat ovarian follicles toward further action by LH or FSH. This refractory state is not complete but relative under physiological conditions. In the rat, the duration of this phenomenon seems to coincide with the slight but significant elevation of follicular cAMP and to last from a few hours after the gonadotropin surge up to ovulation.