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Biol Pharm Bull. 2008 Sep;31(9):1646-50.

Studies on neurosteroids XXV. Influence of a 5alpha-reductase inhibitor, finasteride, on rat brain neurosteroid levels and metabolism.

Author information

1
Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Japan.

Abstract

In this study, we examined the influence of finasteride (FIN), a 5alpha-reductase inhibitor, on the brain levels and metabolism of neurosteroids [allopregnanolone (AP), 3alpha-dihydroprogesterone (3alpha-DHP), progesterone (PROG), 20alpha-dihydroprogesterone and 11-deoxycorticosterone (DOC)] in rats exposed to immobilization stress. For this purpose, the sensitive, reproducible and accurate liquid chromatography-electrospray ionization-tandem mass spectrometric (LC-ESI-MS/MS) methods that enable the quantification of trace amounts of brain neurosteroids were first developed. The animal study using these methods demonstrated that FIN dose-dependently inhibits the stress-induced elevation of the brain AP, a potent positive modulator of the gamma-aminobutyric acid (GABA) type A receptors, and a 10 mg/kg dose of FIN can almost completely deplete AP in the brains. The study also found that the 20alpha-reduction of PROG is enhanced when its 5alpha-reduction pathway is inhibited in the brains. No change was found in the brain levels of 3alpha-DHP, another GABAergic neurosteroid, and DOC by the administration of FIN.

PMID:
18758053
DOI:
10.1248/bpb.31.1646
[Indexed for MEDLINE]
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