title: Inhibition of 5alpha-reductase in rat prostate reveals differential regulation of androgen-response gene expression by testosterone and dihydrotestosterone.
abstract: The growth and development of some of the male sex accessory organs such as the prostate requires the conversion of testosterone to dihydrotestosterone (DHT) by 5alpha-reductase. To provide insights into the role of testosterone versus DHT in the prostate, we studied the impact of finasteride, a potent and specific inhibitor of 5alpha-reductase, on the expression of prostatic androgen-response genes in testis-intact rats and in 7-day castrated rats. Finasteride inhibition of the conversion of testosterone to DHT was confirmed by measuring serum and intraprostatic androgens. As expected, finasteride treatment caused a reduction in the wet weight of the prostate in the testis-intact rats and inhibited the testosterone-stimulated prostatic regrowth in the 7-day castrated rats. Although finasteride treatment had little or no effect on the expression of the surveyed androgen-response genes in testis-intact rats, its administration enhanced the expression of many androgen-response genes during the testosterone-stimulated regrowth of the regressed prostate in castrated rats. These observations suggest that testosterone is more potent than DHT in stimulating the expression of many androgen-response genes in the regressed prostate. The expression of androgen-response genes is mainly prostate specific and thus is likely to be associated with androgen-dependent prostatic differentiation. Therefore, testosterone is more potent than DHT in inducing differentiation and weaker in stimulating proliferation during prostate regrowth. The fact that testosterone is a strong inducer of prostatic differentiation has potential clinical implications.
authors.affiliation: Department of Urology, Northwestern University Medical School, Chicago, IL 60611, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Dadras
authors.forename: X
authors.initials: X
authors.lastname: Cai
authors.forename: I
authors.initials: I
authors.lastname: Abasolo
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000818:Animals; D013196:Dihydrotestosterone / Q000378:metabolism*; D004357:Drug Synergism; D018120:Finasteride / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009919:Orchiectomy; D009929:Organ Size; D011467:Prostate / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements / Q000235:genetics*; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D058891:5-alpha Reductase Inhibitors; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D013739:Testosterone; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase