Estradiol is selectively neurotoxic to hypothalamic beta-endorphin neurons

• Published in: Endocrinology (Philadelphia) Vol. 132; no. 1; p. 86
• Main Authors: Desjardins, G C, Brawer, J R, Beaudet, A
• Format: Journal Article
• Language: English
• Published: United States 01.01.1993
• Subjects: Animals; Arcuate Nucleus of Hypothalamus - cytology; Arcuate Nucleus of Hypothalamus - drug effects; beta-Endorphin - metabolism; Cell Count; Enkephalin, Methionine - metabolism; Estradiol - pharmacology; Female; Hypothalamus - cytology; Hypothalamus - drug effects; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neuropeptide Y - metabolism; Neurotensin - metabolism; Rats; Rats, Wistar; Somatostatin - metabolism; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0013-7227
• DOI: 10.1210/en.132.1.86

The neurotoxic effects of estradiol on hypothalamic arcuate neurons were examined in a model of chronic estrogenization induced by means of a single injection of estradiol valerate (EV). Eight weeks after EV treatment, a 60% decrease in the total number of beta-endorphin-immunoreactive neurons was detected in the arcuate nucleus. In contrast, the numbers of neurotensin-, somatostatin-, and tyrosine hydroxylase-immunoreactive neurons were unchanged, suggesting that the effects of estradiol were selective for beta-endorphin neurons. Further evidence for the selectivity of estradiol's actions was provided by RIAs indicating decreases in hypothalamic beta-endorphin concentrations, but not in Metenkephalin or neuropeptide-Y concentrations. Cell counts performed in Nissl-stained material using unbiased stereological methods revealed a reduction in the total number of neurons in the EV-treated group compared to that in the controls. The estimated number of neurons lost (approximately 3500) corresponded precisely with the total number of beta-endorphin neurons lost (approximately 3600), as estimated using quantitative immunocytochemistry. These results confirm the selectivity of estradiol's effect on the beta-endorphin cell population and demonstrate that the observed decrease in beta-endorphin immunoreactivity reflects actual cell loss. The evidence indicates that the selective neurotoxic effect of estradiol on hypothalamic beta-endorphin neurons contributes to reproductive senescence, suggesting that steroids may participate in disruption of the biological functions that they normally facilitate.