The 21-aminosteroid antioxidant, U74389F, prevents estradiol-induced depletion of hypothalamic beta-endorphin in adult female rats

Brain Res. 1994 Jul 25;652(1):161-3. doi: 10.1016/0006-8993(94)90332-8.


A single intramuscular injection of 2 mg estradiol valerate (EV) results in neuronal degeneration and beta-endorphin depletion in the hypothalamic 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-induced beta-endorphin depletion in the hypothalami of adult female rats. Neither EV nor 21-aminosteroid treatment had any effect on hypothalamic concentrations of neuropeptide Y and Met-enkephalin, confirming that the estradiol lesion is fairly selective for the beta-endorphin cell population. The present findings support the hypothesis that the toxic effect of estradiol on hypothalamic beta-endorphin neurons is mediated by free radicals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Enkephalin, Methionine / metabolism
  • Estrogen Antagonists / pharmacology*
  • Female
  • Hypothalamus / cytology
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism*
  • Neurons / drug effects
  • Neuropeptide Y / metabolism
  • Pregnatrienes / pharmacology*
  • Rats
  • beta-Endorphin / metabolism*


  • Antioxidants
  • Estrogen Antagonists
  • Neuropeptide Y
  • Pregnatrienes
  • U 74389F
  • Enkephalin, Methionine
  • beta-Endorphin