Recent in vivo and in vitro studies suggest that retinoic acid receptor (RAR)-mediated processes may be involved in androgen regulation of prostate cells in a manner that may be altered during prostatic carcinogenesis. We tested this hypothesis in the newly established carcinoma and non-carcinoma rat prostate epithelial cell lines, NRP-154 and NRP-152, respectively. In DMEM/F-12 medium supplemented with 10% charcoal stripped fetal calf serum (cFCS), the number of both NRP-152 and NRP-154 cells were stimulated by testosterone (T), with a 4-fold greater effect in NRP-152 than in NRP-154 cells. Retinoic acid (RA) alone also stimulated the growth of NRP-152 cells, but failed to induce cell growth of NRP-154 cells. Importantly, the level of RAR alpha mRNA was elevated whereas the levels of RAR gamma and androgen receptor (AR) mRNA were lower in NRP-154 cells compared to those in NRP-152 cells. Treatment of NRP-152 cells with increasing doses of T resulted in a dose-dependent decrease and rebound of the level of RAR alpha and gamma mRNA in NRP-152 cells; these effects were not apparent, if not reversed, in NRP-154 cells. Both ligand binding and Western blot analyses revealed that epidermal growth factor receptor (EGF-R) was stimulated by 20 nM T but was suppressed by 0.1 microM RA, which also attenuated the stimulating effects of T on EGF-R in NRP-152 and to a lesser extent in NRP-154 cells. The differences in the level and androgen regulation of RAR mRNAs and reciprocal regulation of EGF-R expression by T and RA between NRP-154 and NRP-152 cells suggest that variations in the EGF-R and RAR signal events may contribute to differences in growth rate between these two cell lines.