The effects of 17β-estradiol (E), ethinylestradiol (EE), progesterone (P), 5α-dihydroprogesterone (5DHP), 17α-hydroxyprogesterone (17HP), testosterone (T), dihydrotestosterone (DHT) and combinations of P, 5DHP, 17HP with E on the basal release of LH and FSH, as well on the pituitary responses to synthetic LH and FSH-releasing hormone (LH-RH/FSH-RH), were examined in vitro using isolated rat pituitaries. EE in doses of O.OOO16-O.5 μg/ml suppressed release of LH and FSH in response to LH-RH. E in doses of 0.036-0.08 μg/ml augmented the basal level of LH in the medium and rarely that of FSH, but inhibited the release of FSH in response to LH-RH. Stimulation of LH release induced by LH-RH was not potentiated by the smaller doses of estrogens. E in doses of 0.5-25 μg/ml lowered the basal release of LH and FSH, and inhibited the response to LH-RH, FSH release being much more susceptible to this inhibitory effect than LH release. P in doses of 1.1-10 μg/ml did not affect basal release of LH and FSH and a dose of 10 μg/ml was required to inhibit consistently stimulation of LH and FSH release in response to LH-RH. 5DHP and 17HP in doses of 1.1-10 μg/ml lowered the basal release of LH and FSH and suppressed the augmented release of both these gonadotropins in response to LH-RH. The combinations of P, 5DHP or 17HP with E suppressed basal release of FSH and LH, inhibited the stimulatory effect of LH-RH on release of LH and FSH more effectively than either one of these progestogens alone and suppressed the stimulation of LH release more effectively than estrogen alone. However, the LH-RH induced stimulation of FSH release was depressed by estrogen to such a degree that additional inhibitory effect of a progestogen was in most cases blunted. T and DHT greatly inhibited the secretion of both LH and FSH in response to LH-RH, DHT being more effective than testosterone. The results demonstrated that high doses of sex steroids inhibit the response to LHRH/FSH-RH in vitro by an action exerted directly on the pituitary tissue. The metabolites of P and T could participate in the regulation of release of gonadotropins and might, together with estrogen, affect the relative ratio of FSH and LH being secreted.
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