Conjugated equine estrogens reverse the effects of aging on central and peripheral allopregnanolone and beta-endorphin levels in female rats

Abstract

Objective To compare β-endorphin and allopregnanolone levels and their response to a 2-week oral estrogen treatment with conjugated equine estrogens (CEE) in young ovariectomized (ovx) and in healthy aged female rats. Design Prospective study. Setting Animal laboratory in an academic environment. Animal(s) Twenty-four young ovx and 24 healthy aged female Wistar rats were treated with CEE. Three 8-rat control groups (cycling, ovx, and aged rats) were also included. Intervention(s) Treated rats underwent 14-day oral treatment with three doses of CEE: 0.1 mg/kg/day, 0.5 mg/kg/day, and 2 mg/kg/day. Main outcome measure(s) Cerebral and peripheral β-endorphin and allopregnanolone levels. Result(s) Beta-endorphin levels were lower in aged vs. cycling and ovx control rats. In brain and serum allopregnanolone levels were lower in aged vs. cycling control rats, whereas in the adrenals they were higher in aged vs. cycling animals. In the hypothalamus and anterior pituitary allopregnanolone levels were lower in ovx vs. aged animals. In both ovx and aged animals, CEE treatment reverted the effects of ovariectomy and aging, in a dose-dependent manner. Conclusion(s) Aging is associated with a decrease in cerebral and peripheral β-endorphin and allopregnanolone. In hypoestrogenic rats, CEE treatment restores allopregnanolone and β-endorphin content; this indicates a role for these compounds as neuroendocrine mediators of the effects of estrogens.