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


METHODS
Prospective study.


METHODS
Animal laboratory in an academic environment.


METHODS
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.


METHODS
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.


METHODS
Cerebral and peripheral beta-endorphin and allopregnanolone levels.


RESULTS
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.


CONCLUSIONS
Aging is associated with a decrease in cerebral and peripheral beta-endorphin and allopregnanolone. In hypoestrogenic rats, CEE treatment restores allopregnanolone and beta-endorphin content; this indicates a role for these compounds as neuroendocrine mediators of the effects of estrogens.
Genazzani
Andrea R
AR
Department of Reproductive Medicine and Child Development, P. Fioretti Division of Obstetrics and Gynecology, University of Pisa, Via Roma 35, 56100 Pisa, Italy. a.genazzani@obgyn.med.unipi.it
Stomati
Massimo
M
Bernardi
Francesca
F
Luisi
Stefano
S
Casarosa
Elena
E
Puccetti
Simone
S
Genazzani
Alessandro D
AD
Palumbo
Marco
M
Luisi
Michele
M
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000172:deficiency; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000494:pharmacology*; D004971:Estrus; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011280:Pregnanolone / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism*
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D001615:beta-Endorphin; D011280:Pregnanolone