The cAMP analogue, dbcAMP, affects rabbit ovarian cell proliferation, apoptosis, release of steroids and response to hormones.

Abstract

Cyclic adenosine monophosphate (cAMP)-related intracellular mechanisms can be important in the control of reproductive processes. The aim of the present study was to examine possible hormonal and intracellular mechanisms mediating the action of cAMP on ovarian cell functions, in particular the mechanisms of stimulatory action of dbcAMP on rabx and caspase 3), plasma level of progesterone and estradiol, and release of progesterone, testosterone and estradiol by isolated ovarian fragments, as well as the response of these fragments to hormonal regulators of ovarian steroidogenesis--FSH, IGF-I and ghrelin (all at doses of 100 ng/ml). Release of hormones was assessed by RIA. The expression of markers of proliferation and apoptosis was evaluated by electrophoresis-Western blotting. Administration of dbcAMP resulted in a reduction of the estradiol level, but not progesterone level in rabbit plasma, as well as in progesterone and estradiol release, but not testosterone release, by isolated ovarian fragments. Additions of FSH, IGF-I and ghrelin to culture medium reduced the release of progesterone and increased testosterone and estradiol output by fragments isolated from control animals. The release of all these hormones was increased by fragments isolated from dbcAMP-treated animals. Both dbcAMP injections and addition of FSH, IGF-I and ghrelin to culture medium promoted the accumulation of proliferation and apoptosis markers in cultured ovarian fragments, whilst dbcAMP increased the stimulatory effects of hormones on these markers. The present observations (1) confirm involvement of peptide hormones FSH, IGF-I and ghrelin in the control of ovarian cell proliferation, apoptosis and steroid hormone release; (2) demonstrate the involvement of cAMP-dependent intracellular mechanisms in promotion of rabbit ovarian cell proliferation, apoptosis and in regulation of ovarian steroidogenesis; (3) suggest the involvement of cAMP-dependent mechanisms in mediating and/or promoting the effect of peptide hormones FSH, IGF-I and ghrelin on ovarian cell proliferation, apoptosis, but not on steroidogenesis; (4) suggest that the stimulatory action of dbcAMP on rabbit reproduction could be due to dbcAMP-induced changes in ovarian cell proliferation, apoptosis, steroid hormone release and the response of these processes to hormonal regulators.