Finasteride treatment inhibits adult hippocampal neurogenesis in male mice.
BACKGROUND
The 5-alpha-reductase inhibitor finasteride is used for the treatment of androgenic alopecia, benign prostate hyperplasia and prostate cancer. Besides inhibiting the conversion of testosterone to the biologically more active 5alpha-dihydrotestosterone, it also inhibits the production of neurosteroids. Decreased neurosteroid levels are postulated to be involved in the pathophysiology of psychiatric disorders such as depression. As neurosteroids metabolized by 5-alpha-reductase influence neural plasticity, we investigated whether finasteride treatment alters adult hippocampal neurogenesis, implicated in the pathophysiology of depression.


METHODS
Male C57BL/6N mice were treated subchronically (7 days) with finasteride or vehicle. Adult neurogenesis was assessed at two different time points after treatment (day 1; day 35) using immunohistochemistry.


RESULTS
Finasteride treatment led to a significant decrease in brain 5alpha-dihydrotestosterone levels and induced a reversible reduction in the number of newborn cells and young neurons in the hippocampus. 35 days after the last finasteride injection, neurogenesis had returned to normal.


CONCLUSIONS
These data indicate that inhibition of 5-alpha-reductase activity by finasteride treatment influences neuronal plasticity on a structural level. These changes might contribute to the pathophysiology of depressive episodes observed after finasteride treatment.
Römer
B
B
RG Behavioural Biology, Central Institute of Mental Health, Mannheim, University of Heidelberg, Germany. benedikt.roemer@zi-mannheim.de
Pfeiffer
N
N
Lewicka
S
S
Ben-Abdallah
N
N
Vogt
M A
MA
Deuschle
M
M
Vollmayr
B
B
Gass
P
P
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000818:Animals; D001921:Brain / Q000187:drug effects; D001923:Brain Chemistry; D002452:Cell Count; D013196:Dihydrotestosterone / Q000032:analysis; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D018120:Finasteride / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D013739:Testosterone; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase