Document Detail


Evidence for atrophy and apoptosis in the prostates of men given finasteride.
MedLine Citation:
PMID:  8636309     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Finasteride, a 5 alpha-reductase inhibitor, decreases prostate size and improves symptoms in men with benign prostatic hyperplasia. However, little is known about prostate histopathology in men taking finasteride. To determine the mechanism by which finasteride reduces prostate size, tissue was collected at the time of prostatectomy from men taking either no medication (n = 10) or 5 mg finasteride daily for 6-18 days (n = 6; group 1), 23-73 days (n = 5; group 2), or 3 months to 4 yr (n = 5; group 3). To assess whether finasteride causes epithelial atrophy, morphometric measurement of epithelial cell and duct width was used. The mean epithelial cell width in control prostates (mean +/- SEM, 21 +/- 0.7 microns) decreased with duration of treatment to 19 +/- 1 microns in group 1, 15 +/- 2 microns in group 2, and 8 +/- 0.3 microns in group 3. Mean duct width decreased from 135 +/- 6 microns in the control prostates to 128 +/- 10 microns in group 1, 103 +/- 3 microns in group 2, and 63 +/- 6 microns in group 3. To assess whether prostate cell death was occurring, sections were in situ end labeled for DNA breaks and immunostained for tissue transglutaminase (tTG), a marker of apoptosis (programmed cell death). The percentage of epithelial cells staining for DNA breaks was 0.4 +/- 0.2 in control prostates, 2.8 +/- 0.9 in group 1, 1.7 +/- 0.5 in group 2, and 0.7 +/- 0.3 microns in group 3. Anti-tTG staining of epithelial cells was graded on a scale of 0-4. In control prostates, 3 +/- 1% of the ducts were grade 3 or 4 (> 50% of epithelial cells staining). In finasteride-treated prostates, 2 +/- 2% of the prostates in group 1, 13 +/- 4% of the prostates in group 2, and 0.5 +/- 0.5% of the prostates in group 3 were grade 3-4. These results indicate that a progressive decrease in epithelial cell size and function occurs during the first several months in the prostates of men treated with finasteride. The staining for DNA breaks and the tTG staining also indicate that an increased rate of apoptosis is occurring transiently in these prostates. We conclude that finasteride causes prostate involution through a combination of atrophy and cell death.
Authors:
R S Rittmaster; R W Norman; L N Thomas; G Rowden
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  81     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-07-08     Completed Date:  1996-07-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  814-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Atrophy
DNA / drug effects
Dihydrotestosterone / metabolism
Double-Blind Method
Enzyme Inhibitors / pharmacology*
Epithelium / pathology
Finasteride / pharmacology*,  therapeutic use
Humans
Male
Placebos
Prostate / drug effects*,  metabolism,  pathology
Prostatic Hyperplasia / drug therapy
Testosterone 5-alpha-Reductase / antagonists & inhibitors
Transglutaminases / analysis
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Placebos; 521-18-6/Dihydrotestosterone; 9007-49-2/DNA; 98319-26-7/Finasteride; EC 1.3.99.5/Testosterone 5-alpha-Reductase; EC 2.3.2.13/Transglutaminases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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