Androgen-induced biochemical responses in epithelium lacking androgen receptors: characterization of androgen receptors in the mesenchymal derivative of urogenital sinus.

Heterotypic tissue recombinants, composed of adult bladder epithelium obtained from testicular feminization syndrome mice (TfmBLE) and embryonic wild-type rat urogenital sinus mesenchyme (UGM) were grown as subcapsular renal grafts in male athymic nude mice for 30 days. The resultant prostatic tissue that developed was subjected to extensive biochemical analyses for androgen receptors. From previous autoradiographic studies it was shown that UGM possesses androgen receptors and induces the TfmBLE to form prostatic ductal-acinar epithelium that lacks androgen receptors. The purpose of the present study is to biochemically characterize the mesenchymal androgen receptors. According to results obtained by autoradiographic analyses, androgen receptors are expressed in the mesenchyme of tissue recombinants. Cytosolic androgen receptors analyzed by the Scatchard method utilizing R-1881 as a ligand showed that the dissociation constant (Kd) of androgen receptors localized within the mesenchyme of the tissue recombinants differs from that found in the mouse prostate gland, but resembles that found in the rat ventral prostate (VP). Sucrose density gradient analysis of the cytosol androgen receptors showed the presence of 8 S [3H]dihydrotestosterone (DHT) binding component under the low salt condition. The mesenchymal androgen receptors are capable of translocating efficiently from cytosol to nuclear compartment, seemingly unaffected by adjacent TfmBLE. The quantity of both cytosol and nuclear androgen receptors expressed in tissue recombinants is only about 1/3 of that found in the rat VP and is in agreement with the morphometric analysis of tissue recombinants, which indicated that about 1/3 of the cells in the tissue recombinants are stromal cells. These results extend previous autoradiographic results and further suggest that androgen receptors present in the mesenchymal compartment may be necessary for the expression of androgen-elicited responses in the TfmBLE that lacks androgen receptors. In addition, this study confirms a novel model system for the study of mesenchymal androgen receptors in tissues unmolested by mechanical or enzymatic dissociation.