Testosterone 5α-reductase and the accumulation of dihydrotestosterone in benign prostatic hyperplasia

Cowan, Robert A.; Cook, B.; Cowan, Sheila K.; Grant, J. K.; Sirett, D.A.N.; Wallace, Andrew M.

doi:10.1016/0022-4731(79)90089-x

Cited by 19 publications

(14 citation statements)

References 14 publications

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“…Therefore, the interpretation of the data of Table 1 with respect to their possible biological relevance is problematical. Similar dis¬ crepancies were reported by others (Sirett et al 1980) and it is not improbable that, mainly due to differences in the methodological procedures, our RIA data on homogenates of epithelium and stroma are only in part identical to those of other groups (Cowan et al 1979;Sirett et al 1980;Bruchovsky et al 1980;Bolton et al 1981). An alternative approach to compare the accumu¬ lation of DHT in the epithelium and stroma of BPH and normal prostate would seem to be the measurement of DHT in the nuclei.…”

Section: Discussionsupporting

confidence: 86%

“…Androgen metabolism (Harper et al 1974;Cowan et al 1977Cowan et al , 1979Bruchovsky et al 1980;Romijn et al 1980;Krieg et al 1980Krieg et al , 1981, androgen and oestrogen binding (Bashirelahi et al 1980;Sirett et al 1980;Krieg et al 1981) and endogenous tissue DHT levels (Bruchovsky et al 1980;Sirett et al 1980;Bolton et al 1981) have been investigated in both compartments of BPH. With respect to androgen metabolism, most investigators came to stroma than in the epithelium of BPH, while in the normal prostate (Bruchovsky et al 1980;Krieg et al 1981) this difference is less pronounced.…”

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confidence: 97%

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Endogenous androgen levels in epithelium and stroma of human benign prostatic hyperplasia and normal prostate

Bartsch¹,

Krieg²,

Becker³

et al. 1982

Acta Endocrinologica

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5\g=a\-Dihydrotestosterone (DHT) and 5\g=a\-androstane-3\g=a\, 17\g=b\-diol(3\g=a\-diol) were extracted from epithelium and stroma of human benign prostatic hyperplasia (BPH) and of normal prostate and quantified by RIA. The main results were: (1) concerning the BPH, DHT is mainly located in the nuclear fraction of epithelium and stroma, whereas 3\g=a\-diolwas completely of extranuclear origin, (2) in the nuclei derived from BPH stroma the DHT content (7.1 \ m=+-\0.88 pmol/mg DNA, mean \m=+-\sem [n = 14]) was significantly higher (P < 0.01) than in the nuclei derived from BPH epithelium (3.8 \ m=+-\ 0.38 pmol/ mg DNA [n = 14]). The DHT content in the nuclear fraction derived from unseparated, i.e. whole tissue, was 5.6 \m=+-\0.60 pmol/mg DNA [n = 14], (3) the biological significance of the overwhelming DHT accumulation in the stromal nuclei for the BPH tissue is reflected by a significant correlation between the DHT values in the nuclei from stroma and whole tissue (rs = 0.710, P < 0. 01) and (4) in four normal prostates the DHT content in the nuclear fraction of epithelium (1.3 \m=+-\0.37

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Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 97%

Endogenous androgen levels in epithelium and stroma of human benign prostatic hyperplasia and normal prostate

Bartsch¹,

Krieg²,

Becker³

et al. 1982

Acta Endocrinologica

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“…Human prostatic stroma has the ability to metabolize testosterone to 5a-DHT (Prout, Kliman, Daly, Maclaughlin & Griffin, 1976), and in preparations of separated cells from human BPH tissues, 5a-reductase has also been shown to be predominantly associated with the stroma (Cowan et al 1977;Cowan, Cook, Cowan, Grant, Sirett & Wallace, 1979).…”

Section: Introductionmentioning

confidence: 97%

Distribution and Concentrations of Androgens in Epithelial and Stromal Compartments of the Human Benign Hypertrophic Prostate

Bolton¹,

Lahtonen²,

Hammond³

et al. 1981

Journal of Endocrinology

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Prostate tissues removed from patients with benign prostatic hypertrophy were separated into epithelia and stromal components and the concentrations of testosterone, 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, 4-androstene-3,17-dione, 5 alpha-androstanedione and androsterone in these two fractions were determined by radioimmunoassays after the purification of solvent steroid extracts by Lipidex-5000 column chromatography. On a 'per cell' basis (i.e. relative to DNA), testosterone was equally distributed between the two components, while the other androgens measured were more abundant in the stroma. The observation that 5 alpha-reduced androgens (especially 5 alpha-dihydrotestosterone) were more concentrated in the stroma, and that significant correlations between concentrations of metabolically related androgens were more common in the stroma than in the epithelium, indicate that the stroma is an important site of androgen metabolism in benign prostatic hypertrophic tissues. The present data also support the suggestion that 5 alpha-dihydrotestosterone produced in the prostatic stroma may be transferred to the epithelium by way of sex hormone binding globulin in the extracellular spaces of the prostate.

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“…Cowan et al (1979) found epithelium to have more affinity to endogenous DHT than the stroma. Our own findings support this hypothesis.…”

Section: A-dihydrotestosteronementioning

confidence: 95%

“…The stromal-epithelial interaction has been stud¬ ied recently by various authors (Cowan et al 1977(Cowan et al , 1979Lakey et al 1979;Wilkin et al 1980;Romijn et al 1980;Krieg et al 1981). After separation of epithelial and stromal cells, the authors found in BPH as well as in normal prostate a high 5a-reductase activity located mainly in the stroma.…”

Section: A-dihydrotestosteronementioning

confidence: 95%

Microautoradiographic studies on distribution of 5α-dihydrotestosterone, cyproterone acetate and oestradiol-17β in human prostatic hyperplasia tissue transplanted to juvenile rats

Ruberg¹,

Senge

Neumann³

1982

Acta Endocrinologica

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While maintaining the actual conditions prevailing in benign prostatic hyperplasia (BPH) in man, transplantation of BPH tissue to newborn rats proved a suitable model for examining the distribution of sexual hormones in different tissue compartments of BPH. In combination with the microautoradiographic method, it was possible to demonstrate the residence of the radioactive androgen 5\g=a\-dihydrotestosterone (5\g=a\-DHT),the antiandrogen cyproterone acetate (CA) and the oestrogen oestradiol-17\g=b\(E2) in the epithelium and/or stroma of human BPH tissue. Quantitative evaluation in the form of a point per area count on photographic pictures yielded a silver grain distribution ratio in epithelium and stroma of 1.3:1 and 1.5:1 for epithelium to stroma after administration of [3H]5\g=a\-DHT and [3H]CA administration respectively and 0.5:1 after [3H]E2. The high tracer recovery rate throughout the stroma following E2 administration supports the current view that the stromal proliferation is attributable mainly to oestrogen influences. The relatively high silver particle proportion throughout the stroma following 5\g=a\-DHTadministration corroborates recent findings which suggest that the exclusive androgen dependency of the glandular epithelium can only be considered in conjunction with an active metabolization of androgens in the stroma. The correspondence in the distribution of the radioactive tracer after [3H]5\g=a\-DHT and [3H]CA administration both in the epithelium and stroma suggests that an antagonism may also exist in the stroma.In the healthy prostate, a balanced ratio exists between the number of secretory glandular cells and the amount of adjacent stroma, the two entities forming a functional unit. In prostatic hyperplasia this unit is disturbed. Normal growth and the coordinated division of adjacent epithelial and stroma cells is abolished, the cells divide indepen¬ dent of their neighbour, grow and form a new system of deviating organ structure (Hechter 1975). Both the epithelium of the glandular ducts and acini and the muscular and fibrous stroma are involved in every conceivable combination in the hyperplastic changes, although the individual organ elements are largely preserved -morpho¬ logically, the adenomatous glandular cell, for example, displays no definite qualitative differen¬ ces in comparison to the normal glandular cell (Kirchheim & Bacon 1968).A major requirement in searching for models to simulate in animals the hyperplastic changes which take place in the human prostate is to preserve as far as possible the unit formed by the glandular epithelium and stroma. The model of transplan¬ ting human prostatic tissue to neonatal rats (also referred to henceforth as heterotransplantation), only recently developed by Senge et al. (1970, 1972) and Richter et al. (1971), presents a prac¬ ticable alternative to animal models and tissue cultures.The aim of this study was to investigate the distribution of dihydrotestosterone, cyproterone acetate and oestradiol in BPH tissue by means of heterotranspl...

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Testosterone 5α-reductase and the accumulation of dihydrotestosterone in benign prostatic hyperplasia

Cited by 19 publications

References 14 publications

Endogenous androgen levels in epithelium and stroma of human benign prostatic hyperplasia and normal prostate

Endogenous androgen levels in epithelium and stroma of human benign prostatic hyperplasia and normal prostate

Distribution and Concentrations of Androgens in Epithelial and Stromal Compartments of the Human Benign Hypertrophic Prostate

Microautoradiographic studies on distribution of 5α-dihydrotestosterone, cyproterone acetate and oestradiol-17β in human prostatic hyperplasia tissue transplanted to juvenile rats

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