Augmentative and inhibitory effects of chronic steroid injections on LH release and their dependency on time

The effect of daily s.c. injections of 50 μg ethinyl estradiol, 1 mg norethindrone and of 1 mg megestrol acetate upon basal and LH-RH-stimulated LH release was investigated in intact female rats. Basal serum LH was rapidly depressed by ethinyl estradiol and norethindrone, while megestrol acetate was less effective. The pituitary response to 30 or 150 ng LH-RH was initially augmented by the treatment with norethindrone reaching a maximum after 5 days, by ethinyl estradiol with a maximum after 10 days, and megestrol acetate after 20 days. In every case, the positive effect was followed by inhibition of H-RH mediated LH release when treatment with the respective steroid was continued. Two weeks after discontinuing of the daily injections, the blockade of the pituitary was abolished. It is concluded that a rapid decrease of endogenous LH-RH release is responsible for the suppression of basal serum LH, while a concomitant direct action on the pituitary augments the response to exogenous LH-RH during the first days of steroid application. When the treatment with steroids is continued for a prolonged period of time, the pulsatile pattern of LH-RH release from the hypothalamus becomes impaired, and this results in dependency on the type of steroid in inhibiting of pituitary response.