Studies on Neurosteroids XXV. Influence of a 5.ALPHA.-Reductase Inhibitor, Finasteride, on Rat Brain Neurosteroid Levels and Metabolism

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.