THE 21-AMINOSTEROID ANTIOXIDANT, U74389F, PREVENTS ESTRADIOL-INDUCED DEPLETION OF HYPOTHALAMIC BETA-ENDORPHIN IN ADULT FEMALE RATS

A single intramuscular injection of 2 mg estradiol valerate (EV) resul ts in neuronal degeneration and beta-endorphin depletion in the hypoth alamic arcuate nucleus of adult female rats. We have hypothesized that peroxidase-positive astrocytes in this brain region oxidize estrogens and catecholestrogens to semiquinone radicals which mediate oxidative neuronal injury. In the present study, dietary administration of the potent antioxidant 21-aminosteroid, U-74389F, completely blocked EV-in duced beta-endorphin depletion in the hypothalami of adult female rats . Neither EV nor 21-aminosteroid treatment had any effect on hypothala mic concentrations of neuropeptide Y and Met-enkephalin, confirming th at the estradiol lesion is fairly selective for the beta-endorphin cel l population. The present findings support the hypothesis that the tox ic effect of estradiol on hypothalamic beta-endorphin neurons is media ted by free radicals.