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5 alpha-reductase inhibition by finasteride (Proscar) in epithelium and stroma of human benign prostatic hyperplasia. 1994

H Weisser, and S Tunn, and M Debus, and M Krieg
Institute of Clinical Chemistry and Laboratory Medicine, University Clinic Bergmannsheil, Bochum, Germany.

Finasteride is a specific 5 alpha-reductase inhibitor that has been shown to reduce the size of human benign prostatic hyperplasia (BPH) by inhibiting the intraprostatic conversion of testosterone to 5 alpha-dihydrotestosterone. The aim of the present in vitro study was to describe in more detail the inhibitory effect of finasteride on 5 alpha-reductase in epithelium and stroma of human BPH. 5 alpha-Reductase activity in epithelium and stroma was inhibited dose-dependently by finasteride. The mean IC50 (50% inhibitory concentration) values, determined in the presence of various testosterone concentrations, were generally 2- to 4-fold lower in epithelium than in stroma. With finasteride concentrations greater than 5 nM, competitive inhibition of 5 alpha-reductase occurred both in epithelium and stroma. The mean inhibition constant Ki[nM +/- SEM] was 7 +/- 3 and 31 +/- 3 in epithelium and stroma, respectively. In the presence of finasteride concentrations < or = 5 nM, the epithelial 5 alpha-reductase seems to be inhibited in an uncompetitive manner, whereas such low finasteride concentrations cause either no inhibition (1-2 nM) or competitive inhibition (5 nM) in stroma. Our present study provides evidence that the inhibitory effect of finasteride on 5 alpha-reductase is much stronger in epithelium than in stroma. Therefore, it is conceivable that the global size-reduction of BPH under finasteride treatment is primarily due to the regression of BPH epithelium.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011470 Prostatic Hyperplasia Increase in constituent cells in the PROSTATE, leading to enlargement of the organ (hypertrophy) and adverse impact on the lower urinary tract function. This can be caused by increased rate of cell proliferation, reduced rate of cell death, or both. Adenoma, Prostatic,Benign Prostatic Hyperplasia,Prostatic Adenoma,Prostatic Hyperplasia, Benign,Prostatic Hypertrophy,Prostatic Hypertrophy, Benign,Adenomas, Prostatic,Benign Prostatic Hyperplasias,Benign Prostatic Hypertrophy,Hyperplasia, Benign Prostatic,Hyperplasia, Prostatic,Hyperplasias, Benign Prostatic,Hypertrophies, Prostatic,Hypertrophy, Benign Prostatic,Hypertrophy, Prostatic,Prostatic Adenomas,Prostatic Hyperplasias, Benign,Prostatic Hypertrophies
D004848 Epithelium The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body. Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000369 Aged, 80 and over Persons 80 years of age and older. Oldest Old
D017154 Stromal Cells Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. Cell, Stromal,Cells, Stromal,Stromal Cell
D058891 5-alpha Reductase Inhibitors Drugs that inhibit 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE. They are commonly used to reduce the production of DIHYDROTESTOSTERONE. 3-Oxo-5-alpha-Steroid 4-Dehydrogenase Inhibitor,5-alpha Reductase Inhibitor,Steroid 5-alpha-Reductase Inhibitor,Testosterone 5-alpha-Reductase Inhibitor,3-Oxo-5-alpha-Steroid 4-Dehydrogenase Inhibitors,Steroid 5-alpha-Reductase Inhibitors,Testosterone 5-alpha-Reductase Inhibitors,3 Oxo 5 alpha Steroid 4 Dehydrogenase Inhibitor,3 Oxo 5 alpha Steroid 4 Dehydrogenase Inhibitors,4-Dehydrogenase Inhibitor, 3-Oxo-5-alpha-Steroid,4-Dehydrogenase Inhibitors, 3-Oxo-5-alpha-Steroid,5 alpha Reductase Inhibitor,5 alpha Reductase Inhibitors,5-alpha-Reductase Inhibitor, Steroid,5-alpha-Reductase Inhibitor, Testosterone,5-alpha-Reductase Inhibitors, Steroid,5-alpha-Reductase Inhibitors, Testosterone,Inhibitor, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase,Inhibitor, 5-alpha Reductase,Inhibitor, Steroid 5-alpha-Reductase,Inhibitor, Testosterone 5-alpha-Reductase,Inhibitors, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase,Inhibitors, 5-alpha Reductase,Inhibitors, Steroid 5-alpha-Reductase,Inhibitors, Testosterone 5-alpha-Reductase,Reductase Inhibitor, 5-alpha,Reductase Inhibitors, 5-alpha,Steroid 5 alpha Reductase Inhibitor,Steroid 5 alpha Reductase Inhibitors,Testosterone 5 alpha Reductase Inhibitor,Testosterone 5 alpha Reductase Inhibitors
D018120 Finasteride An orally active 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE inhibitor. It is used as a surgical alternative for treatment of benign PROSTATIC HYPERPLASIA. Chibro-Proscar,Eucoprost,MK-906,Propecia,Propeshia,Proscar,Chibro Proscar,MK 906,MK906

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