ANDROGEN AND ESTROGEN RESPONSIVENESS OF STROMAL CELLS DERIVED FROM THE HUMAN HYPERPLASTIC PROSTATE - ESTROGEN REGULATION OF THE ANDROGEN RECEPTOR

Stromal cells derived fi-om collagenase-digested benign hyperplastic a dult prostates were isolated and grown in culture. Androgen and oestro gen receptor status were determined and growth in response to mibolero ne (a synthetic androgen) and oestradiol-17 beta was measured. In addi tion, the ability of oestrogens to regulate the androgen receptor in s tromal cells was investigated. [H-3]Thymidine incorporation into DNA w as stimulated by mibolerone in primary and secondary cultures, but sen sitivity was lost with subsequent passages. Androgen stimulation of [H -3]thymidine incorporation was consistently inhibited by the anti-andr ogen cyproterone acetate. Oestradiol-17 beta also stimulated [H-3]thym idine incorporation into DNA, and this effect was inhibited by the ant i-oestrogen tamoxifen. Sensitivity to oestradiol was lost with subsequ ent passages. A combination of mibolerone and oestradiol was not syner gistic in increasing [H-3]thymidine incorporation into DNA, but maxima l stimulation occurred at 100-fold lower concentrations of mibolerone and oestradiol when the two hormones were applied in combination. Spec ific high-affinity [H-3]mibolerone- and [3H]oestradiol-binding sites w ere demonstrated by radioligand binding in intact cells. The affinity for oestradiol binding to its receptor exceeded that quantified for mi bolerone binding to the androgen receptor, whilst the number of oestra diol-binding sites was approximately tenfold less than that quantified for mibolerone. Treatment with oestradiol down-regulated the number o f [H-3]mibolerone binding sites 1.7-fold (P<0.005) as early as day 2 a fter oestradiol treatment. In conclusion, we successfully cultured str omal cells derived from hyperplastic prostates which retained sensitiv ity to androgen and oestrogen. These results suggest that mibolerone a nd oestradiol exert their biological effects independently of each oth er, but there is a close relationship in which one steroid increases t he sensitivity of the other in the stromal cells of the hyperplastic p rostate.