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) 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.
Department of Anatomy and Cell Biology, Bloomfield Centre for Research in Aging, Jewish General Hospital, McGill University, Montreal, Que., Canada.
H M
HM
Schipper
G C
GC
Desjardins
A
A
Beaudet
J R
JR
Brawer
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects; D009478:Neuropeptide Y / Q000378:metabolism; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D001615:beta-Endorphin / Q000378:metabolism*
D000975:Antioxidants; D004965:Estrogen Antagonists; D009478:Neuropeptide Y; D011281:Pregnatrienes; C074965:U 74389F; D004744:Enkephalin, Methionine; D001615:beta-Endorphin