Comparison of testosterone, 5α-dihydrotestosterone and 5α-androstane-3β,17β-diol metabolisms in human normal and hyperplastic prostates

Morfin, Robert; Stefano, S. Di; Bercovici, J. P.; Floch, H.H.

doi:10.1016/0022-4731(78)90157-7

Cited by 42 publications

(11 citation statements)

References 15 publications

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“…The studies reported here agree closely with those published previously (Shimazaki, Kurihara, Ito & Shida, 1965;Chamberlain, Jagarinec & Ofner, 1966;Jenkins & McCaffery, 1974;Farnsworth & Brown, 1976 Bercovici & Flock, 1978). The results suggest that the metabolism of testosterone in the prostatic tissue pursues two distinct and opposing path¬ ways: (a) a two-step reductive pathway involving the NADPH-dependent 5oc-reduction of the substrate to 5a-DHT, followed by a further reduction to the androstanediol epimers; (b) an oxidative pathway responsible for the conversion of testosterone to androstenedione.…”

Section: Discussionsupporting

confidence: 93%

Effects of Tamoxifen on the Binding and Metabolism of Testosterone by Human Prostatic Tissue and Plasma in Vitro

Habib¹,

Rafati²,

Robinson³

et al. 1979

Journal of Endocrinology

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The in-vitro metabolism of testosterone in benign and malignant prostatic tissue was examined and distinct quantitative differences between the two types of specimens were observed. The major metabolite of testosterone in the hyperplastic prostate was 5 alpha-dihydrotestosterone and a high 3 alpha(beta)-hydroxysteroid dehydrogenase activity was also detected. In the malignant tissue, 5 alpha-reductase activity was considerably reduced and there was little or no androstanediol formed; the 17 beta-dehydrogenase activity was, however, higher than in the benign tissue. The decrease in 5 alpha-reductase was always followed by a compensatory change in the 3 alpha(beta)-hydroxysteroid dehydrogenase of the malignant prostate. The present study revealed that the ratio of the mean activities of 5 alpha-reductase to 3 alpha(beta)-hydroxysteroid dehydrogenase in the two types of specimen always remained a constant. Although the antioestrogen, tamoxifen, induced an inhibitory effect on the activities of 5 alpha-reductase and 17 beta-hydroxysteroid dehydrogenase in the gland, the present investigation also suggested that tamoxifen stimulated the activity of 3 alpha(3 beta)-hydroxysteroid dehydrogenase. In blood, the action of tamoxifen appeared to be confined to the displacement of androgens from the binding sites on the sex hormone binding globulin.

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Section: Discussionsupporting

confidence: 93%

Effects of Tamoxifen on the Binding and Metabolism of Testosterone by Human Prostatic Tissue and Plasma in Vitro

Habib¹,

Rafati²,

Robinson³

et al. 1979

Journal of Endocrinology

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“…Therefore, according to Bolton et al [18], DHT levels are still somewhat higher in BPH than in normal prostates, but by a much smaller amount than previously thought. The continuing probability of increased levels of DHT in BPH versus normal prostates is still very appealing and logical, since there are numerous studies including those of Krieg et al [14], Morfin et al [19], Bruchovsky et al [12], and Isaacs et al [20] that show an increase in Sol-reductase enzyme activity in the BPH compared with the normal prostate. All well-controlled published studies support this finding unequivocally; in addition, Isaacs et al [20] found significantly less 17P-hydroxysteroid oxidase and 3a-hydroxysteroid reductase in BPH patients versus normals.…”

Section: Dht Represents 90% or More Of The Steroid Bound In The Promentioning

confidence: 99%

Pathogenesis and medical treatment of benign prostatic hyperplasia

Geller

1989

Prostate

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Tissue concentrations of dihydrotestosterone (DHT) and the enzymes that regulate its level, such as 5α‐reductase, appear to play a major role in the pathogenesis of benign prostatic hyperplasia (BPH). This argument is strongly supported by the objective decreases in prostate size and improvement in symptoms of prostatism that occur following androgen withdrawal. A variety of androgen‐withdrawal therapies for BPH have been reported since the early 1900s. Although success in the treatment of BPH has been claimed for all of them, including surgical castration, medical castration with progestational antiandrogens, gonado‐tropin‐releasing hormone (GNRH)‐agonist castration, or androgen‐receptor blockade with pure antiandrogens such as flutamide, very few studies, until recently, have provided convincing objective evidence for therapeutic efficacy in BPH. Recently, magnetic resonance imaging (MRI) scanning and ultrasound have become available to quantify objective changes in prostate volume and have indisputably demonstrated that androgen withdrawal does significantly decrease prostate size. The consequences of this on clinical symptoms of prostatism are currently under study. Studies of the effect of 5α‐reductase inhibitors on prostatism are in progress. They hold promise for future treatment of BPH since they may decrease prostate size and DHT concentration without any effect on sexual function.

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“…The capacity of the human prostate to metabolize testosterone into biologically more 'active' metabolites is well established (Morfin, Di Stefano, Bercovici & Floch, 1978;Bruchovsky & Lieskowsky, 1979;Habib, Rafati, Robinson & Stitch, 1979; Krieg, Bartsch, Janssen & Voigt, 1979;Lasnitzki, 1979;Habib, 1980). Probably the most critical transformation by the prostate is the NADPH-dependent 5a-reduction of testosterone to dihydrotestosterone and this is usually followed by a further reduction to the androstanediol epimers.…”

Section: Introductionmentioning

confidence: 99%

Androgen Metabolism in the Epithelial and Stromal Components of the Human Hyperplastic Prostate

Habib¹,

Tesdale²,

Chisholm³

et al. 1981

Journal of Endocrinology

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The reduced and oxidized metabolites of testosterone and dihydrotestosterone were measured in the stromal and epithelial components of 23 human hyperplastic prostates. Our studies indicate differences in the hormonal metabolic patterns of the stroma and epithelium of the resected specimens when compared with tissues obtained retropubically. Testosterone 5 alpha-reductase was evenly distributed between the two components of the specimens obtained retropubically whereas the 3 alpha (beta)-hydroxysteroid dehydrogenase was predominantly located in the stroma. The measurements on the resected specimens suggest, on the other hand, that the bulk of the 5 alpha reductase and 3 alpha (beta)-hydroxysteroid dehydrogenase activities were confined to the stroma although these activities were considerably lower than those measured in the corresponding components of the retropublically obtained specimens. The conversion of testosterone to androstenedione was negligible in all the samples analysed. We therefore conclude that the stroma is the main site for the transformation of dihydrotestosterone to the androstanediol epimers and that the asymmetric distribution of the 3 alpha (beta)-hydroxysteroid dehydrogenase may be instrumental in the development of hyperplasia in the prostate gland. Furthermore, the results of this study indicate that electroresection impairs the enzymatic activities of the tissue.

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Comparison of testosterone, 5α-dihydrotestosterone and 5α-androstane-3β,17β-diol metabolisms in human normal and hyperplastic prostates

Cited by 42 publications

References 15 publications

Effects of Tamoxifen on the Binding and Metabolism of Testosterone by Human Prostatic Tissue and Plasma in Vitro

Effects of Tamoxifen on the Binding and Metabolism of Testosterone by Human Prostatic Tissue and Plasma in Vitro

Pathogenesis and medical treatment of benign prostatic hyperplasia

Androgen Metabolism in the Epithelial and Stromal Components of the Human Hyperplastic Prostate

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