Selective effect of chlormadinone acetate on brain allopregnanolone and opioids content.
BACKGROUND
Synthetic progestins may have different biological actions depending on the target tissue, the dose administered or the coadministration of an estrogen molecule. The purpose of the present study was to evaluate the neuroendocrine effect of chlormadinone acetate (CMA) administration, analyzing the brain content of allopregnanolone (ALLO), an endogenous neurosteroid gamma-aminobutyric acid agonist with anxiolytic properties, and the brain level of beta-endorphin (beta-END), an endogenous opioid implicated in pain mechanism, emotional state and autonomic control.


METHODS
Seven groups of Wistar ovariectomized (OVX) rats received one of the following treatments: oral CMA at a dose of 0.1, 0.5 or 1 mg/kg per day; estradiol valerate (E(2)V) at a dose of 0.05 mg/kg per day; CMA plus E(2)V (CMA 0.1 or 0.5 or 1 mg/kg per day + E(2)V 0.05 mg/kg per day) for 14 days. One group of fertile rats and one group of OVX rats were used as controls.


RESULTS
CMA increased ALLO content in the hippocampus and, when it was administered with E(2)V, also in the hypothalamus and anterior pituitary, evidence of a synergic effect with estrogens only in selective brain areas. beta-END content increased in the neurointermediate lobe and anterior pituitary after CMA administration, and it did not antagonize the positive, estrogen-induced increase of beta-END level.


CONCLUSIONS
CMA is effective in increasing ALLO and beta-END in selective brain areas showing a specific pattern of interaction with brain function, different compared to progesterone or to other synthetic progestins. In particular, CMA action on part of the limbic system (hippocampus and hypothalamus) and on the anterior pituitary support the hypothesis that this progestin might affect cognitive function, emotional state and autonomic control.
Pluchino
Nicola
N
Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics, University of Pisa, 56100 Pisa, Italy.
Lenzi
Elena
E
Merlini
Sara
S
Giannini
Andrea
A
Cubeddu
Alessandra
A
Casarosa
Elena
E
Begliuomini
Silvia
S
Luisi
Michele
M
Cela
Vito
V
Genazzani
Andrea Riccardo
AR
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002715:Chlormadinone Acetate / Q000494:pharmacology*; D003270:Contraceptive Agents / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D010052:Ovariectomy; D011280:Pregnanolone / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000819:agonists*; D001615:beta-Endorphin / Q000097:blood*
D003270:Contraceptive Agents; D011980:Receptors, Progesterone; D002715:Chlormadinone Acetate; D004958:Estradiol; D001615:beta-Endorphin; D011280:Pregnanolone