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 the regulation of uterine epithelial DNA synthesis by P was investigated by analyzing the four types of tissue recombinants prepared with uterine 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 (E2) stimulated DNA synthesis in all four types of tissue recombinants. On the other hand, P inhibited E2-induced 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-negative) stroma (PRKO-S + wt-E or PRKO-S + PRKO-E). These results clearly demonstrate that the inhibitory effect of P on uterine epithelial DNA synthesis is mediated by stromal PR. Epithelial PR is neither necessary nor sufficient for P inhibition of E2-induced epithelial DNA synthesis.