STROMAL AND EPITHELIAL-CELLS FROM RAT VENTRAL PROSTATE DURING ANDROGEN DEPRIVATION AND ESTROGEN-TREATMENT .2. REGULATION OF TRANSCRIPTION

To identify the functional capacities of prostatic tissue, the expression of steroid hormone receptors, growth factors, oncogenes and particular enzymes was studied at the RNA level in isolated stromal and epithelial cells of rat ventral prostate (RVP) under different hormonal conditions (androgen deprivation, estrogen treatment). Slot blot and Northern blot analyses of isolated RNA resulted in characteristic changes: In the control prostate, androgen receptor (AR) mRNA was high in epithelium of intact prostate, but low in stroma. Its level was increased after castration in the epithelium during the initial 24 hours, whereas an only slight increase occurred in stroma after one week castration. The AR signal was not altered by estradiol treatment in epithelium and stroma. Conversely, the estrogen receptor (ER) mRNA, predominant in stroma and very low in epithelium, decreased after castration in stroma and epithelium within 24 hours and was absent one week later. After estrogen treatment the ER signal increased considerably in stroma. mRNA of both basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta) were exclusively found in stroma. Both were low in controls and responded in a different way to castration and estrogen treatment within 24 hours. bFGF was increased in estrogen-treatment animals, while TGF-beta was induced by castration. Shortly after castration (2 hours) v-fos expression increased and reached a maximum after 6 hours, but was no more detectable after 12 hours in epithelium. c-neu (oncogene homologue of the human erbB2) mRNA, on the other hand, low in control animals (in stroma), did not change during the initial 24 hours, but increased mRNA levels were observed after one week. DNase I increased only in epithelium of castrated animals, but not in estrogen-treated animals. Although no attempts have been made to relate our results exclusively to either androgen withdrawal or estrogenisation, a differential regulation of prostatic stroma and epithelium is suggested: during estrogen treatment the functional capacities of stroma are depressed, while estrogen responsivity is increased. Conversely, androgen withdrawal results in fibrous transformation of the gland through stromal activation.