In vitro studies of the regulation of androgen-tissue relationship in normal canine and hyperplastic human prostate

Slices from canine prostate were superfused with [17alpha-3H] testosterone and 5alpha-dihydro[1,2-3H]testosterone at 'physiological' concentrations; to some wuperfusions, either [3H]cyproterone or [3H]cyproterone acetate was also added. The following parameters were measured: 'uptake' of anti-androgen by the tissue, rate of entry of testosterone and 5alpha-dihydrotestosterone into the tissue, rate of efflux from the tissue of 5alpha-dihydrotestosterone and concentration of 'diffusible' 5alpha-dihydrotestosterone in the slices. The adsorption of steroids on to the surface of the slices and the bulk flow of tritiated water into the slices were also investigated. It was concluded that these two factors did not interfere with the measurement of entry and efflux of the androgens. Cyproterone and cyproterone acetate were not metabolized, but were concentrated in the slices to many times the level in the medium. With rate of supply of anti-androgens up to 43 pmol/min, their uptake increased together with the rate of entry of the two androgens and the rate of efflux of 5alpha-dihydrotestosterone. At a higher rate of supply of anti-androgens, their uptake and the rates of entry and efflux of the androgens decreased sharply. In most cases, the inward movement of 5alpha-dihydrotestosterone into the slices took place against a negative concentration gradient, while that of testosterone always occurred down a positive concentration gradient. These results confirmed the hypothesis already put forward that 'carriers' involved in the transport of androgens are present in the membrane of prostatic cells (Giorgi, Moses, Grant, Scott & Sinclair, 1974). Non-specific and specific intracellular binding, exhibiting greater affinity for 5alpha-dihydrotestosterone than for testosterone, was demonstrated in canine prostate by means of 'washing-out' experiments. On the basis of its affinity for androgens and the presence of inhibition by low concentrations of anti-androgen, intracellular binding seemed to be due to components distinct from the postulated membrane 'carriers'.

supporting

confidence: 91%

supporting

confidence: 89%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Studies on Androgen Transport Into Canine Prostate in Vitro

Giorgi¹

1976

“…Three observations have to be taken into con¬ sideration. First, it has been suggested that the limited capacity of hyperplastic tissue to regulate the uptake and removal of androgens (Giorgi et al 1971; Giorgi, Moses, Grant, Scott «fe Sinclair, 1974) might be due to an excessive number of non-specific binding sites in the hypertrophie cell (Giorgi et al 1974). This possibility warrants serious appraisal in view of the demonstrations of both low-and high-affinity binding sites in human prostatic tissue (Hansson, Tveter, Attramadal «fe Torgersen, 1971;Mainwaring & Milroy, 1973;Steins, Krieg, Hollmann «fe Voigt, 1974;Mobbs, Johnson «fe Connolly, 1975;Rosen, Jung, Baulieu «fe Robel, 1975;Cowan, Cowan, Giles «fe Grant, 1976;Hawkins, Nijs & Brassinne, 1977;Menon, Tananis, McLoughlin & Walsh, 1977).…”

Section: -8±4-7mentioning

confidence: 98%

INCREASED RATIO OF 5α-Reductase: 3α(β)-Hydroxysteroid DEHYDROGENASE ACTIVITIES IN THE HYPERPLASTIC HUMAN PROSTATE

Bruchovsky¹,

Lieskovsky²

1979

The activities of 5 alpha-reductase and 3 alpha (beta)-hydroxysteroid dehydrogenase were assayed in homogenates of eight normal, 21 hyperplastic and four carcinomatous human prostates. Samples consisting of 300--500 microgram tissue protein in Tris buffer, pH 7.0, were incubated at 37 degrees C for 30 min in the presence of 50 nM-[3H]androgen and an NADPH-generating system started with 5 X 10(-4)M-NADP. The yield of 5 alpha- and 3 alpha-reduced metabolites, as established by using t.l.c. and g.l.c., gave an estimate of enzyme activity. The formation of metabolites denoting 5 alpha-reductase activity in normal, hyperplastic and carcinomatous tissue respectively was 28.8 +/- 47 (S.E.M.), 76.8 +/- 8.9 and 3.5 +/- 0.7 pmol 30 min-1 mg protein-1; similarly, that denoting 3 alpha (beta)-hydroxysteroid dehydrogenase activity was 69.3 +/- 6.7, 46.6 +/- 5.7 and 38.8 +/- 22.1 pmol 30 min-1 mg protein-1. In all normal prostates 5 alpha-reductase activity was lower than 3 alpha (beta)-hydroxysteroid dehydrogenase activity. Conversely, in 18 out of 21 hyperplastic prostates, 5 alpha-reductase activity was higher than 3 alpha (beta)-hydroxysteroid dehydrogenase activity. The effect of the increase in 5 alpha-reductase activity without a compensatory change in 3 alpha (beta)-hydroxysteroid dehydrogenase activity was to alter the mean ratio between 5 alpha-reductase and 3 alpha (beta)-hydroxysteriod dehydrogenase activities from 0.47 +/- 0.11 in the normal prostate to 1.84 +/- 0,19 in hyperplastic tissue. It is inferred that this change may predispose the hyperplastic prostate to asymmetrical rates of androgen metabolism and thereby contribute to the abnormal accumulation of dihydrotestosterone.

“…Among others, Siiteri & Wilson (1970) and Giorgi, Moses, Grant, Scott & Sinclair (1974) have reported biochemical differences between normal and hyperplastic prostate. The former group found higher concentrations of 5<x-dihydrotestosterone (DHT) but not of testosterone or androst-4-ene-3,17-dione in the diseased tissue.…”

Section: Introductionmentioning

confidence: 96%

Prostatic Distribution of Sex Hormone-Binding Globulin and Cortisol-Binding Globulin in Benign Hyperplasia

Cowan¹,

Cowan²,

Giles³

et al. 1976

Sex hormone-binding globulin-(SHBG) and cortisol-binding globulin-(CBG) like proteins have been demonstrated in prostatic tissue surgically removed from patients with benign prostatic hyperplasia. These proteins are not easily removed by superfusion of tissue slices. Epithelial tissue was separated from stroma and found not to contain the SHBG- or CBG-like proteins. Substantial amounts of these proteins, however, remained associated with the stroma. It is suggested that they may be constituents of interstitial fluid in this tissue compartment. The possible significance of this in benign prostatic hyperplasia is discussed.