Studies on androgen transport into canine prostate in vitro

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'.