Dihydrotestosterone in prostatic hypertrophy

Gloyna, Robert E.; Siiteri, Pentti K.; Wilson, Jean D.

doi:10.1172/jci106392

Cited by 160 publications

(14 citation statements)

References 17 publications

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“…The 3a-diol effect on the acinar parenchyma of the prostate is completely abolished by CA, as monitored by prostatic weight, biochemical analyses and microscopic examin¬ ation. The biochemical determinations of DNA, RNA and zinc content re¬ vealed significantly decreased values comparable to those found in castrated dogs (Gloyna et al 1970;Mackenzie et al 1962). These biochemical events are apparently conditioned by glandular atrophy as shown histologically.…”

Section: Zinc Contentsupporting

confidence: 66%

“…No cellular hypertrophy was demonstrable on meas¬ uring the RNA to DNA ratio compared with the intact control. Gloyna et al (1970) observed cellular hypertrophy after long term administration of DHT in castrated dogs, as measured by RNA to DNA ratio, whereas they found no prostatic hyperplasia but only restoration to normal weights (Gloyna et al 1970). In castrated rats the RNA to DNA ratio returned to normal values after a stimulation period of 10 days with 3a-diol, while epithelial cells were restored to 65% of normal total numbers (de Klerk et al 1975).…”

Section: Zinc Contentmentioning

confidence: 99%

“…A more striking effect was produced when 3«-diol was given in combination with 17/?-oestradiol (OeL>). In contrast to these findings testosterone and dihydrotestosterone (DHT) had failed to induce BPH under similar conditions (Gloyna et al 1970;Wilson et al 1975), although DHT was found to be the major steroid bound to nuclear chromatin in the prostate (Anderson 8c Liao 1968; Bruchovsky 8c Wilson 1968). Furthermore, the concentrations of DHT in hypertrophic prostates in dog and man were significantly greater than in normal glands (Geller el al.…”

mentioning

confidence: 96%

“…Furthermore, the concentrations of DHT in hypertrophic prostates in dog and man were significantly greater than in normal glands (Geller el al. 1976;Gloyna et al 1970;Siiteri 8c Wilson 1970). These results suggest that the accumulation of DHT alone seems not to be the causal mechanism for prostatic growth and that the reduced DHT-metabolite 3a-diol may possibly be involved in the development of BPH.…”

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confidence: 99%

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Biochemical and Histological Studies on Prostates in Castrated Dogs After Treatment With Androstanediol, Oestradiol and Cyproterone Acetate

Tunn

Senge

Schenck

et al. 1979

Acta Endocrinologica

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The effect of cyproterone acetate (CA) on experimentally induced benign prostatic hyperplasia (BPH) in the castrated dog was investigated. BPH was induced by 6 months' treatment with 3\g=a\-androstanediol (3\g=a\-diol) alone and in combination with 17\g=b\-oestradiol(Oe2). RNA, DNA and zinc content of the glands were determined in addition to histological examination and measurement of the prostates. Two different types of prostatic enlargement were observed. First, 3\g=a\-diolinduced typical diffuse canine hyperplasia with replacement of functional activity. DNA, RNA and the zinc content of total glands were increased compared with intact controls.

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Section: Zinc Contentsupporting

confidence: 66%

Section: Zinc Contentmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 99%

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Biochemical and Histological Studies on Prostates in Castrated Dogs After Treatment With Androstanediol, Oestradiol and Cyproterone Acetate

Tunn

Senge

Schenck

et al. 1979

Acta Endocrinologica

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“…Benign prostatic hyperplasia is known to occur spontaneously in two species, man and dog. While there are several anatomical and histological differences between human and canine benign prostatic hyperplasia, the condition in dog has many features in common with the human disease (1)(2)(3). The pathogenesis remains incompletely understood in either species; however, evidence for an endocrine role is well established.…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance imaging of the efficacy of specific inhibition of 5α‐reductase in canine spontaneous benign prostatic hyperplasia

Cohen

Taber

Malatesta

et al. 1991

Magnetic Resonance in Med

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A leading role for prostatic levels of dihydrotestosterone (DHT) in the pathogenesis of benign prostatic hyperplasia is well established, if incompletely understood. The present study provides initial confirmation that 5 alpha-reductase inhibition alone is sufficient to prevent prostatic accumulation of DHT and to produce epithelial regression in the canine prostate. In dogs treated with the specific 5 alpha-reductase inhibitor finasteride, prostatic volume decreased to one-third of the baseline volume, while the prostatic concentration of DHT fell fivefold: both were constant in placebo control dogs. Demonstration that MR imaging can serve as accurate modality to assess prostatic volume was provided by serial measurements of the canine prostate and by correlation of the last imaging measurement with the weight of the excised prostate. Significant intensity changes were observed in T2-weighted images measured post-treatment; these changes correlated with the histopathology of the prostate. These results suggest that beyond quantifying regression, multiecho T2 measurements can be useful in probing accompanying changes occurring on the cellular level.

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Identification and partial characterization of two steroid 5α-reductase isozymes in the canine prostate

et al. 1998

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BACKGROUND The dog has been extensively used as an in vivo model to test the pharmacokinetics and effects on pathological prostatic growth of 5α‐reductase inhibitors. However, no information is available on the existence or characteristics of canine 5α‐reductase isozymes. METHODS The 5α‐reduction of testosterone is analyzed in dog prostatic homogenates. Three human‐specific inhibitors are tested for their activity against dog 5α‐reductase. RESULTS Two pH optima of 5α‐reductase activity in dog prostatic homogenates are described, comparable to the pH optima of rat and human 5α‐reductase isozymes. Kinetic analysis of 5α‐reductase enzymatic activity at pH 7.0 revealed isozymes with a low apparent affinity constant (Km = 2.67 nM) and a high apparent affinity constant (Km = 1.23 μM). These apparent affinity constants compare favorably to the human and rat isozymes types II and I, respectively. The human type II inhibitor finasteride selectively inhibited the low Km isozyme, whereas the human type I inhibitor MK386 preferentially inhibited the high Km isozyme. The human type I inhibitor LY306089 was nonspecific for the dog isozymes. CONCLUSIONS We postulate that the high and low Km isozymes described here represent the dog type I and type II 5α‐reductase isozymes, respectively. Prostate 34:222–230, 1998. © 1998 Wiley‐Liss, Inc.

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Dihydrotestosterone in prostatic hypertrophy

Cited by 160 publications

References 17 publications

Biochemical and Histological Studies on Prostates in Castrated Dogs After Treatment With Androstanediol, Oestradiol and Cyproterone Acetate

Biochemical and Histological Studies on Prostates in Castrated Dogs After Treatment With Androstanediol, Oestradiol and Cyproterone Acetate

Magnetic resonance imaging of the efficacy of specific inhibition of 5α‐reductase in canine spontaneous benign prostatic hyperplasia

Identification and partial characterization of two steroid 5α-reductase isozymes in the canine prostate

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