Influence of the 5 α-reductase inhibitor type 2 on circulating neuroactive steroids
Michaela Duskova1, Martin Hill1, Miroslav Hanus2, Michaela Matouskova2 & Luboslav Starka1
The 5α-reductase is one of the enzyme of steroid synthesis and founded in two isoformes. Two distinct 5α-reductase isoenzymes, type I and type II, are found across mammalian species. Each of these isoenzymes is differentially expressed in tissues and during distinct developmental stages and also in different species. The 5α-reductase is enzyme responsible for the reduction of testosterone to dihydrostestosterone, progesterone to dihydroprogesterone and deoxycorticosterone to dihydrodeoxycorticosterone. These steroids and their metabolites (termed neuroactvive steroids) have rapid non-genomic effects on brain function and behavior, primarily via an enhancement of γ-aminobutyric acid (GABA)ergic inhibitory neurotransmission. Neuroactive steroids have through GABA receptor anticonvulsant, antidepressant and anxiolytic effects. Finasteride is the first 5α-reductase type II inhibitor that was introduced to clinical practice in 1992 for the treatment of benign prostatic hyperplasia in the dose of 5 mg/day and few years later for androgentic alopecia in dose of 1 mg/day. There are some reports suggesting finasteride induction of depressive symptoms and anxiety in human. The steroid profile of patients treated by finasteride was detected only in analyse of urine (it was strikingly similar to that of male pseudohermaphrodites with inherited 5 alpha-reductase deficiency). In our study a group of 32 men (12 men with androgenetic alopecia and 20 men wih bening prostatic hyperplasia) was examined. In all individual, their hormonal profile of steroids hormones in blood was determined. Finasteride in the daily dose of 1 mg (men with androgenetic alopecia) or 5 mg (men with benign prostatic hyperplasia) was administrated for 4 months. After the treatment the same hormonal profile was determined. In addition to the decrese of dihydrotestosterone level after treatement, the alteration in other 5 alfa steroids metabolites was found, which could explain the depresive symptomatology.
The study was supported by grant No.NR/8525 5 of the IGA MZCR.