Steroid hormones modulate the production of nitric oxide and cGMP in the rat uterus

Previously, we demonstrated the presence of an L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway in the rat uterus and that NO inhibits contractility during pregnancy but not during delivery. In the present study, we investigated the possible role of sex steroid hormones in the regulation of NO synthesis and cGMP generation. NO, measured as nitrite production, and cGMP were determined in full thickness uterine tissues from either pregnant rats on different gestational days or nonpregnant animals after treatment with steroid hormones. NO formation was low in tissues from nonpregnant rats, substantially increased during pregnancy and decreased during labor and immediately postpartum. The cGMP content in the same tissues followed a similar trend. Uterine nitrite production and cGMP levels from animals treated with estradiol and estradiol + progesterone were significantly lower compared to those treated with vehicle or progesterone. These data provide strong evidence that the NO-cGMP system is upregulated during pregnancy to maintain uterine quiescence and a rise in estrogen at term could inhibit this system and thus initiate labor.