Elevated intranuclear dihydrotestosterone in prostatic hyperplasia of aging dogs

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

“…Sa-Dihydrotestosterone at micromolar concentrations displayed the most significant and consistent mitogenic activity in the findings presented by these investigators. Other workers [26] have reported that both experimentally-induced and spontaneously arising canine BPH are associated with an elevation of intranuclear concentrations of Sa-dihydrotestosterone and parallel increases in intranuclear androgen receptor concentration. No correlation between prostate growth and intracellular 5a-androstane-3a, 170-diol concentration has been demonstrated [26].…”

“…Other workers [26] have reported that both experimentally-induced and spontaneously arising canine BPH are associated with an elevation of intranuclear concentrations of Sa-dihydrotestosterone and parallel increases in intranuclear androgen receptor concentration. No correlation between prostate growth and intracellular 5a-androstane-3a, 170-diol concentration has been demonstrated [26]. A preliminary analysis of cytosol receptor proteins (not shown) in the CAPE 1 cell line has shown androgen-binding components with a high affinity for 5a-dihydrotestosterone similar to that demonstrated in intact canine prostates both in this laboratory [27] and elsewhere [14].…”

“…However, comparisons of these findings in addition to observations made in this laboratory (unpublished) also reveal shifts in the 3a-hydroxysteroid oxido-reductase system between the formation of 5a-dihydrotestosterone and the formation of Sa-androstane-3a,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.…”

“…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. The anomalous lack of prostatic cell growth rate stimulation in the presence of exogenous 5a-dihydrotestosterone observed in our studies, at the concentrations used, is paralleled in other investigations [20,22].…”

Phenotypic modulation of the canine prostate after long‐term treatment with androgens and estrogens

“…The hormonal mechanisms underlying both spontaneous and experimental prostatic hyperplasia in the dog were studied by Meikle et a1 [27], Moore et a1 [29], Dube et a1 [ 1 1, 121, and Ehrlichman et a1 [ 131. It was shown in these studies that experimental prostatic hyperplasia produced by the injection of androgens probably occurred via increased androgen receptor levels [ 121 and supranormal nuclear DHT concentration Walsh and Wilson [39] and Ehrlichman et a1 [13] found a synergistic enhancement of prostatic growth in estradiol plus DHT-treated dogs.…”