Metabolism and binding in vitro of 5α-androstane-3β, 17β-diol and of 5α-androstane-3α, 17β-diol in cell fractions of rat ventral prostate and liver

Epithelial and fibroblastoid cell lines derived from the normal canine prostate. II. Cell proliferation in response to steroid hormones

“…While it is accepted that steroid entry into cellular cytoplasm is by passive diffusion, recent findings [32] in the regenerating rat prostate indicate that the intranuclear accumulation of non-receptor-bound 5a-dihydrotestosterone is a controlled process in which the maximum capacity of the nuclear pool for non-receptor-bound Sa-dihydrotestosterone is defined, and the rate of entry of the steroid limited. This observation, in addition to the relatively high levels of 3cx-hydroxysteroid dehydrogenase activity demonstrated in prostatic nuclei [30], suggests the interesting possibility that the biological activity of 5a-androstane-3a, 17P-diol may be mediated via effects on the nuclear pool of non-receptor-bound Sa-dihydrotestosterone.…”

“…However, comparisons of these findings in addition to observations made in this laboratory (unpublished) also reveal shifts in the 3a-hydroxysteroid oxido-reductase system between the formation of 5a-dihydrotestosterone and the formation of Sa-androstane-3a, 17P-diol that are dependent on prevailing individual steroid concentrations and the availability of cofactors (NADPH). It is, therefore, difficult to establish whether the elevated intracellular concentrations of 5a-dihydrotestosterone associated with BPH [26,30] are a consequence of increased rate of oxidation of 5a-androstane-3a, 17P-diol or decreased reduction rate of Sa-dihydrotestosterone, both events resulting in a net accumulation of 5a-dihydrotestosterone. These results in addition to the relative increase in the concentration of intranuclear androgen receptors associated with the development of BPH [26] suggest that the effects of Sa-androstane-3a, 17P-diol on cell proliferation observed in this and other studies may not be mediated directly by the interaction of this steroid with receptor proteins, but indirectly by a mechanism resulting in the accumulation of intracellular Sa-dihydrotestosterone.…”