Dydrogesterone increases allopregnanolone in selected brain areas and in serum of female rats.
OBJECTIVE
To investigate the effects of dydrogesterone (DYD), a synthetic progestin largely used in hormone therapy, on the central nervous system by studying two markers of the neuroendocrine function: the neurosteroid allopregnanolone and the opioid beta-endorphin.


METHODS
Experimental study on animal model.


METHODS
Academic research environment.


METHODS
72 Wistar female rats.


METHODS
One group of fertile and one of ovariectomized rats (receiving placebo) were used as control. After ovariectomy, the rats underwent a 2-week oral treatment of DYD (0.2, 0.6, or 1.0 mg/kg per day), alone or with estradiol valerate (E2V; 0.05 mg/kg per day).


METHODS
Allopregnanolone and beta-endorphin, assessed in different brain areas and in circulation.


RESULTS
Ovariectomy decreased allopregnanolone anywhere except in the adrenal gland and reduced beta-endorphin central levels; E2V reversed the effects of ovariectomy; and DYD (1 mg/kg per day) increased allopregnanolone levels in frontal lobe, hippocampus, and hypothalamus. Combined administration of DYD at 1 mg/kg per day plus E2V determined a further increase of allopregnanolone levels in frontal lobe, hippocampus, hypothalamus, and serum. Dydrogesterone did not modify the levels of beta-endorphin induced by E2V.


CONCLUSIONS
Dydrogesterone interacts with allopregnanolone levels (less with beta-endorphin), and it can be considered important modulator of the neuroendocrine function.
Pluchino
Nicola
N
Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy.
Lenzi
Elena
E
Casarosa
Elena
E
Cela
Vito
V
Begliuomini
Silvia
S
Ninni
Filippo
F
Freschi
Letizia
L
Luisi
Stefano
S
Genazzani
Andrea Riccardo
AR
D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D004394:Dydrogesterone / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D010052:Ovariectomy; D011280:Pregnanolone / Q000097:blood* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D001615:beta-Endorphin / Q000378:metabolism
D004958:Estradiol; D001615:beta-Endorphin; D004394:Dydrogesterone; D011280:Pregnanolone