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

Abstract

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.

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

“…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.…”

“…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.…”

The Endocrinology and Developmental Biology of the Prostate*

“…Although it is unclear whether androgen receptors are elevated in one or the other cell fraction, both cell types are now accepted as bona fide androgen targets (86,180, [186][187][188][189][190][191][192]. Estrogen and progestin receptors have also been detected in both epithelium and stroma (173,189).…”

Androgen concentrations in epithelial and stromal cell nuclei of human benign prostatic hypertrophic tissues

“…Our previous studies (Bolton, Lahtonen, Hammond & Vihko, 1981) indicated that 5a-reduced androgens (especially 5a-dihydrotestosterone) are more concentrated in the stromal than in the epithelial part of the human benign hypertrophie prostate.…”

“…The tissues were separated into epithelium and stroma as described previously by Cowan, Cowan, Giles & Grant (1976) and by ourselves (Bolton et al 1981). The buffer used was a modified Krebs-Ringer buffer (Williams & Gorski, 1973) and the separation was mechanical.…”