TIME-DEPENDENT DECREASE OF PITUITARY RESPONSE TO LH-RH AFTER CHRONIC TREATMENT OF INTACT FEMALE RATS WITH ETHINYLOESTRADIOL AND NORETHINDRONE

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Abstract
The effect of daily injections of 50 .mu.g ethinylestradiol and 1 mg norethindrone upon basal and LH-RH[luliberin]-stimulated LH [lutropin] release was investigated in intact adult female rats during a 30 day period. Basal plasma LH was depressed by about 30% during the whole time of steroid treatment, and returned to the level of the control values 2 wk after discontinuation. The injection of 30 ng and 150 ng LH-RH into untreated rats resulted in a significant increase of plasma LH which was, however, not dose-dependent. After the treatment with ethinylestradiol and norethindrone for 5 days, the pituitary response to 150 ng was approximately 4 times higher than that to 30 ng. The LH release after injection of 150 ng LH-RH decreased significantly with the duration of steroid treatment, and was totally abolished by 30 days; whereas 2 wk after the termination of steroid application the pituitary responded to LH-RH in the same manner as in control rats. When 30 ng LH-RH were injected into estrogen/norethindrone treated rats, no decrease in LH release was found until day 20 of the experiment. By 30 days of treatment no rise in plasma LH could be elicited. The activity of the LH-RH-degrading enzyme L-cystine arylamidase was stimulated during the treatment with ethinylestradiol and norethindrone in the pituitary by approximately 100%, whereas almost no effect on this enzyme was seen in the hypothalamus. Chronic treatment of intact female rats with ethinylestradiol and norethindrone causes time-dependent and reversible alterations in the storage of LH in the pituitary. The elevated activity of the LH-RH-degrading enzyme in the pituitary is possibly involved in these processes and/or in the mechanism responsible for the depression of basal LH.