Effects of the new generation selective estrogen receptor modulator EM-652 and oral administration of estradiol valerate on circulating, brain, and adrenal beta-endorphin and allopregnanolone levels in intact fertile and ovariectomized rats.
OBJECTIVE
To investigate the effects of oral estradiol valerate (EV); EM-652, a new-generation selective estrogen receptor modulator; and both agents on central and peripheral beta-endorphin (beta-EP) and allopregnanolone levels in fertile and ovariectomized rats.


METHODS
Prospective study.


METHODS
Animal laboratory in an academic research environment.


METHODS
Thirteen groups of eight Wistar female rats received oral EV (0.01 or 0.05 mg/kg of body weight daily), EM-652 (0.1, 1, or 5 mg/kg daily), or EV (0.05 mg/kg daily) and EM-652 (0.1, 1, or 5 mg/kg/daily) for 14 days.


METHODS
beta-Endorphin levels content in the hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma were measured. Allopregnanolone levels in the hypothalamus, hippocampus, anterior pituitary, adrenal glands, and serum were measured.


METHODS
beta-Endorphin and allopregnanolone levels.


RESULTS
In ovariectomized rats, administration of EV or EM-652 reverses changes in beta-EP and allopregnanolone levels induced by ovariectomy. Administration of EM-652 plus EV prevents the increase in beta-EP and allopregnanolone levels induced by EV in the hippocampus, hypothalamus, and pituitary but not in the adrenal glands and serum.


CONCLUSIONS
In ovariectomized rats, EM-652 has an estrogen-like action that becomes antiestrogenic in the presence of EV administration. In fertile animals, EM-652 exerts estrogen-like or slight antiestrogenic effects.
Bernardi
Francesca
F
Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynacology, University of Pisa, Pisa, Italy.
Stomati
Massimo
M
Luisi
Stefano
S
Pieri
Matteo
M
Labrie
Fernand
F
Riccardo Genazzani
Andrea
A
D000284:Administration, Oral; D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004357:Drug Synergism; D004958:Estradiol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D005260:Female; D005298:Fertility / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D010052:Ovariectomy; D010880:Piperidines / Q000494:pharmacology*; D010902:Pituitary Gland / Q000378:metabolism; D011280:Pregnanolone / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism*
D010880:Piperidines; D020845:Selective Estrogen Receptor Modulators; C012121:ritetronium; D004958:Estradiol; D001615:beta-Endorphin; D011280:Pregnanolone