Androgen dynamics in vitro in the normal and hyperplastic human prostate gland

Abstract

The dynamics of uptake and metabolism in vitro of androgens by normal and hyperplastic human prostate glands was studied by means of a new experimental design proposed by Gurpide & Welch (1969). Prostate slices were perfused with a medium containing [3H]testosterone and [14C]androstenedione, or 5α-dihydro-[3H]testosterone and [14C]testosterone. The entry into the slices, the irreversible metabolism, the conversion between the compounds and the tissue retention or ‘uptake’ of the steroids were measured at the steady state. A similar portion of the three androgens entered the tissue and was irreversibly metabolized. Conversion of testosterone into 5α-dihydrotestosterone was much greater than the interconversion of testosterone and androstenedione. The prostate slices retained 5α-dihydrotestosterone at a concentration three times that in the medium, whereas testosterone and androstenedione were retained to a smaller extent. At a steroid concentration of 0.11μmol/l in the medium, the various parameters did not differ significantly in experiments performed with slices from normal and hyperplastic glands. When the steroid concentration in the medium was increased tenfold, however, a difference between normal and hyperplastic glands was evident. The normal glands increased the uptake and metabolism proportionally to the elevation of the steroid concentration in the medium. In the hyperplastic glands the entry and metabolism lagged behind the increase in steroid supply, whereas the tissue uptake became disproportionately high. The possible causes of this finding are discussed.