Studies on neurosteroids XXV. Influence of a 5alpha-reductase inhibitor, finasteride, on rat brain neurosteroid levels and metabolism.
Level 5 - mechanism / opinion, no new human data
Animal research measuring neurochemical endpoints
PubMed 18758053 · doi:10.1248/bpb.31.1646
What was done
Researchers developed an LC-ESI-MS/MS method to quantify trace brain neurosteroids—allopregnanolone (AP), 3alpha-dihydroprogesterone (3alpha-DHP), progesterone (PROG), 20alpha-dihydroprogesterone, and 11-deoxycorticosterone (DOC). They then evaluated how the 5alpha-reductase inhibitor finasteride affected brain neurosteroid levels and metabolism in rats subjected to immobilization stress.
What was found
Finasteride dose-dependently inhibited the stress-induced surge of brain AP, with a 10 mg/kg dose causing near-complete depletion of AP. When the 5alpha-reduction of PROG was blocked, the 20alpha-reduction pathway of PROG was enhanced. Finasteride treatment produced no detectable changes in brain levels of 3alpha-DHP or DOC. Exact baseline and post-treatment concentrations, sample sizes, and effect sizes were not reported in the abstract.
Why it matters
This study provides mechanistic evidence that finasteride suppresses the central synthesis of allopregnanolone, a major endogenous positive modulator of GABA-A receptors, and reroutes neurosteroid metabolic pathways in the brain during stress.
Limits
The experiment was conducted exclusively in a rat model under acute immobilization stress, which may not mirror human physiology, chronic therapeutic dosing, or basal non-stressed conditions. The abstract omits the number of animals tested, exact quantitative measurements, variances, and behavioral or functional assessments.
Cited by
- supports 5-alpha reductase inhibitors reduce the synthesis of allopregnanolone, which decreases GABAergic neurosteroid signaling.