Ovarian hormone secretory response to gonadotropins and nitric oxide following chronic nitric oxide deficiency in the rat

Ovarian hormone secretion is regulated by gonadotropins, and it has been demonstrated that this response is modulated by nitric oxide (NO). The focus of this study was to determine the effect of chronic NO deficiency on the secretion of ovarian steroids. Female rats were given N-nitro-L-arginine (L-NNA; 0.6 g/L) in their drinking water, and vaginal smears were obtained daily. By 4 wk of treatment, all the rats were in constant estrus or proestrus. At 6-8 wk the animals were killed; the ovaries were removed and incubated in the presence of eCG (1 IU/ml) and hCG (1 IU/ml) and/or S-nitroso-L-acetyl penicillamine (an NO donor, S-NAP; 0.1 mM) for 4 h. Medium was collected at 30 min intervals, and estradiol, progesterone, and androstenedione were measured. Ovaries from proestrous rats served as controls. Ovaries from L-NNA-treated animals had a greater basal and gonadotropin-stimulated release of estradiol but not of androstenedione or progesterone in comparison to ovaries from untreated controls. S-NAP decreased the gonadotropin-stimulated estradiol, progesterone, and androstenedione in ovaries from NO-deficient rats. Steroid secretion in controls was not responsive to S-NAP. We conclude that chronic NO inhibition produces constant estrus due to increased estradiol production and that NO acts to inhibit estradiol and androstenedione production.