Distinct regulation of nitric oxide and cyclic guanosine monophosphate production by steroid hormones in the rat uterus

It has previously been reported that uterine nitric oxide (NO) production i s enhanced during rat pregnancy compared to non-pregnant, labouring or post partum states. The present hypothesis is that these changes in uterine NO p roduction during pregnancy are caused by the interplay of oestrogen and pro gesterone. It is further postulated that changes in cyclic guanosine monoph osphate (cGMP) production closely follow the changes in uterine NO synthesi s. To test these hypotheses a variety of hormonal regimens (17 beta-oestrad iol, progesterone and combinations) were applied to different rat models (p repubertal, non-pregnant intact and ovariectomized as well as pregnant rats ). The production of nitric oxide (NO) as well as basal and in-vitro NO-sti mulated cGMP tissue content were measured in parallel. NO production was me asured by the accumulation of nitrites and nitrates in a 24 h incubation me dium as analysed by Greiss reaction, cGMP content was measured by radioimmu noassay, Diethylenetriamine/NO (DETA/NO) was used as NO donor. NO productio n in the rat uterus was markedly increased by pregnancy compared to other p hysiological (prepubertal, or cycling dioestrus) and experimentally induced (OVX) states. In contrast, uterine cGMP was significantly decreased in pre gnancy. Pregnancy also inhibited the elevation in uterine cGMP after in-vit ro NO challenge. Chronic 17 beta-oestradiol treatment in prepubertal and/or OVX models increased NO production and also mimicked the effect of pregnan cy on cGMP. Administration of progesterone in prepubertal rats induced a pa rallel decrease in both uterine NO and cGMP In conclusion, sex steroid horm ones distinctly regulate uterine NO and cGMP production depending upon the dose and regimen used, as well as the animal's reproductive stale.