Effects of nomegestrol acetate administration on central and peripheral beta-endorphin and allopregnanolone in ovx rats.
The aim of this study was to investigate the effects of nomegestrol acetate (NOMAc) on the central nervous system by analyzing the neurosteroid allopregnanolone and the opioid beta-endorphin (beta-endorphin). 104 Wistar female rats were used in this study; one group of fertile and one group of ovariectomized rats were used as control. The others were ovariectomized and they underwent a 2-week oral treatment of NOMAc (0.05, 0.1, 0.2, 0.5, 1mg/kg/day), alone or with 0.05 mg/kg/day of estradiol valerate (E2V). Allopregnanolone and beta-endorphin were assessed in different brain areas and in circulation. Ovariectomy decreased allopregnanolone anywhere except in the adrenal gland and E2V reversed the effects of ovariectomy. 0.5 and 1mg/kg/day of NOMAc increased allopregnanolone levels in hippocampus. Combined administration of 1mg/kg/day of NOMAc plus E2V induced a further increase of allopregnanolone levels in hippocampus, hypothalamus, and anterior pituitary. NOMAc (1mg/kg/day) decreased the adrenal content of allopregnanolone, both by itself and associated with E2V. NOMAc increased hippocampal and hypothalamic content of beta-endorphin at the highest doses, and it increased positively E2V action, at 1mg/kg/day, also in anterior pituitary and plasma. These findings reinforce the clinical data regarding the capability of NOMAc to modulate the pathways involved in mood and behaviour. In fact, due to the NOMAc action on hippocampus, hypothalamus, and anterior pituitary, our results highlight the selectivity of NOMAc on part of the limbic system and the anterior pituitary, regarding both allopregnanolone and beta-endorphin.
Lenzi
Elena
E
Department of Reproductive Medicine and Child Development, Division of Gynaecology and Obstetrics, University of Pisa, Pisa, Italy.
Pluchino
Nicola
N
Begliuomini
Silvia
S
Ninni
Filippo
F
Freschi
Letizia
L
Centofanti
Manolo
M
Casarosa
Elena
E
Luisi
Stefano
S
Valentino
Valeria
V
Luisi
Michele
M
Genazzani
Andrea Riccardo
AR
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008535:Megestrol / Q000008:administration & dosage / Q000494:pharmacology*; D009649:Norpregnadienes / Q000008:administration & dosage / Q000494:pharmacology*; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011280:Pregnanolone / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D001615:beta-Endorphin / Q000378:metabolism*
D009649:Norpregnadienes; D004958:Estradiol; D001615:beta-Endorphin; C038501:nomegestrol acetate; D011280:Pregnanolone; D008535:Megestrol