STROMAL PROGESTERONE RECEPTORS MEDIATE THE INHIBITORY EFFECTS OF PROGESTERONE ON ESTROGEN-INDUCED UTERINE EPITHELIAL-CELL DEOXYRIBONUCLEIC-ACID SYNTHESIS

The role of epithelial and stromal progesterone (P) receptors(PR) in t he regulation of uterine epithelial DNA synthesis by P was investigate d by analyzing the four types of tissue recombinants prepared with ute rine stroma (S) and epithelium (E) from wild-type (wt) and PR knockout (PRKO)mice:wt-S + wt-E, PRKO-S + PRKO-E, wt-S + PRKO-E, and PRKO-S wt-E. 17-beta estradiol (E-2) stimulated DNA synthesis in all four typ es of tissue recombinants. On the other hand, P inhibited E-2-indueed DNA synthesis only in tissue recombinants prepared with wild-type (PR- positive) stroma (wt-S + wt-E or wt-S + PRKO-E) but not knockout (PR-n egative) stroma (PRKO-S + wt-E Or PRKO-S + PRKO-E). These results clea rly demonstrate that the inhibitory effect of P on uterine epithelial DNA synthesis is mediated by stromal PR. Epithelial PR is neither nece ssary nor sufficient for P inhibition of E-2-induced epithelial DNA sy nthesis.