Reduction of ventral prostate weight by finasteride is associated with suppression of insulin-like growth factor I (IGF-I) and IGF-I receptor genes and with an increase in IGF binding protein 3.
Finasteride, a competitive and specific inhibitor of 5alpha-reductase, is widely used in the treatment of symptomatic benign prostatic hyperplasia. We demonstrate here that finasteride, when administered in an in vivo experimental system, caused ventral prostate regression. Intraprostatic dihydrotestosterone levels decreased, whereas testosterone levels increased in a dose-dependent manner following finasteride treatment. Finasteride also inhibited the expression of insulin-like growth factor (IGF)-I and IGF-I receptor genes in the ventral prostate. Finasteride significantly increased IGF binding protein-3 and slightly decreased IGF binding protein-2, -4, and -5 gene expression. Because IGFs are potent mitogens for prostate epithelial cells, this newly described activity of finasteride may contribute to its antiproliferative properties, particularly with regard to the inhibition of prostate growth seen clinically and in animal models.
Huynh
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Lady Davis Research Institute of the Jewish General Hospital and Department of Surgery, McGill University, Montreal, Quebec, Canada.
Seyam
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RM
Brock
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GB
D058891:5-alpha Reductase Inhibitors; D000818:Animals; D015152:Blotting, Northern; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D018120:Finasteride; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1