Interactions of a phosphodiesterase inhibitor, 3-isobutyl-1-methyl xanthine, with prostaglandin E2, follicle-stimulating hormone, luteinizing hormone, and dibutyryl cyclic 3',5'-adenosine monophosphate (cAMP) in cAMP and steroid production by neonatal rat ovaries in vitro

Abstract

The development of responsiveness to prostaglandin E2 (PGE2), FSH, LH, and [Bu]2cAMP was examined in whole ovaries isolated from neonatal Sprague-Dawley rats on days 0 (birth), 2, 4, or 6 postpartum. Pairs of ovaries were incubated with these stimuli in the absence or presence of 3-isobutyl-1-methyl xanthine (MIX), a potent phosphodiesterase inhibitor, and accumulations in the medium of cAMP, androstenedione, and estradiol were measured. PGE2 stimulated marked cAMP accumulation on day 0 whereas similar responses to FSH and LH did not develop until days 2 and 4, respectively. No cAMP accumulation was detectable in the absence of MIX. Ovaries gradually acquired the ability to produce both cAMP and steroids in response to FSH and LH over the first postnatal week. No steroid accumulation was measurable in incubations conducted on days 0 or 2; however, steroidogenesis was stimulable in day-4 ovaries by (Bu)2cAMP. PGE2, FSH, and LH also stimulated steroid accumulation on day 4, but only when MIX was present in the incubation, suggesting that high levels of endogenous cAMP can also lead to steroid production. By day 6, all stimuli elicited steroid accumulation in a dose-dependent fashion. MIX potentiated the responses to lower doses of these stimuli but not to the higher doses at this age. In the absence of MIX, LH was approximately 100 times more potent than FSH in stimulating steroid production; however, the two gonadotropins were nearly equipotent in this regard when MIX was present in the incubation. These results support the notion that a cAMP-sensitive steroidogenic apparatus is present in the rat ovary as early as the fourth day postpartum. Because of the marked effects of MIX on gonadotropin-induced steroidogenesis, it may be that modulation of phosphodiesterase activity is one way by which steroidogenesis is regulated in the neonatal rat ovary.