Pathologic effect of estradiol on the hypothalamus

• Published in: Biology of reproduction Vol. 49; no. 4; pp. 647 - 652
• Main Authors: BRAWER, J. R, BEAUDET, A, DESJARDINS, G. C, SCHIPPER, H. M
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01.10.1993
• Subjects: Animals; beta-Endorphin - metabolism; Biological and medical sciences; Cell Death - drug effects; Drug toxicity and drugs side effects treatment; Estradiol - pharmacology; Estradiol - toxicity; Female; Humans; Hypothalamic Diseases - chemically induced; Hypothalamic Diseases - pathology; Hypothalamic Diseases - physiopathology; Hypothalamus - drug effects; Hypothalamus - pathology; Luteinizing Hormone - metabolism; Medical sciences; Neurons - drug effects; Pharmacology. Drug treatments; Pituitary Gland - metabolism; Toxicity: nervous system and muscle; Hypothalamic diseases; Toxicity; Arcuate nucleus; Estrogen; Central nervous system; 17β-Estradiol; Neuroendocrine regulation; Review; Mechanism of action; β-Endorphin; Ovarian hormone; Brain (vertebrata)
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod49.4.647

Estradiol provides physiological signals to the brain throughout life that are indispensable for the development and regulation of reproductive function. In addition to its multiple physiological actions, we have shown that estradiol is also selectively cytotoxic to beta-endorphin neurons in the hypothalamic arcuate nucleus. The mechanism underlying this neurotoxic action appears to involve the conversion of estradiol to catechol estrogen and subsequent oxidation to o-semiquinone free radicals. The estradiol-induced loss of beta-endorphin neurons engenders a compensatory increment in mu opioid binding in the medial preoptic area rendering this region supersensitive to residual beta-endorphin or to other endogenous opioids. The consequent persistent opioid inhibition results in a cascade of neuroendocrine deficits that are ultimately expressed as a chronically attenuated plasma LH pattern to which the ovaries respond by becoming anovulatory and polycystic. This neurotoxic action of estradiol may contribute to a number of reproductive disorders in humans and in animals in which aberrant hypothalamic function is a major component.