The aim of this study is to elucidate the role of "beta-endorphin (beta-End) & beta-lipotropin (beta-LPH)" on the regulation of gonadotropin (Gn) secretion. We investigated the relationships between immunoreactive beta-End plus beta-LPH and Gn in peripheral plasma of normal menstruating women, 1) during periovulatory period, especially at the time of Gn surge, 2) at the estrogen induced Gn surge (positive feedback) and 3) at the time of hypoxic stress. Plasma concentrations of beta-End plus beta-LPH were measured as immunoreactive beta-End (i-beta-End) by RIA after extraction with Sep-Pak C18. First, we assessed pulsatile Gn secretions during periovulatory period in 19 normal women every 10 minutes for 4 hours, some women were at the time of Gn surge in its ascending limb, plateau of the peak, and descending limb of the surge. Meanwhile, circadian variations of plasma i-beta-End levels of these subjects were assessed at 4 hours' interval on the same day. In two subjects, on the day before the onset of LH surge, significantly low (p less than 0.05) basal and peak levels of i-beta-End were observed, although the basic patterns of circadian rhythm were preserved. Secondly, changes of plasma i-beta-End levels during estrogen (estradiol benzoate 1mg i.m.) induced positive feedback tests were evaluated in 16 normal women and 6 hypothalamic amenorrheic women by daily blood sampling. In normal subjects, small but significant increases (p less than 0.05) of plasma i-beta-End were observed when Gn showed initial decreases at 48 hours after injection. Subsequently at 72 hours, however, plasma i-beta-End decreased precipitously at the time of Gn surge. On the other hand, in hypothalamic amenorrheic women who were devoid of Gn surge, no significant changes of plasma i-beta-End levels were observed. The transient decreases of plasma i-beta-End just prior to the Gn surge support the idea that i-beta-End exerts tonic inhibition on the onset of Gn surge and the disappearance of its inhibition might trigger the positive Gn surge. And it was also suggested that release mechanisms of both i-beta-End and Gn are impaired in hypothalamic amenorrhea. Thirdly, in acute hypoxic stress experiment, 5 normal female volunteers were placed in hypobaric (500 mbar) condition in which oxygen supply is a half of atmosphere, simultaneous blood samplings of Gn, prolactin and i-beta-End were performed every 15 minutes for 3 hours.(ABSTRACT TRUNCATED AT 400 WORDS)