Paracrine regulation of epithelial progesterone receptor and lactoferrin by progesterone in the mouse uterus

The objective of this study was to determine whether uterine stromal and/or epithelial progesterone receptor (PR) is required for the antagonism by pr ogesterone (P-4) of estradiol-17 beta (E-2) action on expression of PR and lactoferrin in uterine epithelium. Uterine tissue recombinants were prepare d with epithelium (E) and stroma (S) from wild-type (wt) and PR knockout (P RKO) mice: wt-S+wt-E and PRKO-S+wt-E. P-4 action on epithelial PR expressio n was studied in wt-S+wt-E and PRKO-S+wt-E tissue recombinants. E, down-reg ulated epithelial PR in both types of tissue recombinants, but P-4 blocked E-2-induced down-regulation of epithelial PR only in wt-S+wt-E tissue recom binants. Thus, P-4 requires stromal PR to inhibit E-2-induced down-regulati on of epithelial PR. Epithelial PR is not sufficient in itself. The inhibit ory effect of P-4 on lactoferrin expression was studied in 4 types of tissu e recombinants (wt-S+wt-E, PRKO-S+wt-E, wt-S+PRKO-E, and PRKO-S+PRKO-E). E, induced lactoferrin in all 4 types of tissue recombinants. P-4 blocked E-2 -induced lactoferrin expression only in wt-S+wt-E tissue recombinants. In w t-S+PRKO-E tissue recombinants, P-4 inhibited lactoferrin expression only p artially. P-4 failed to block E-2-induced lactoferrin expression in PRKO-Swt-E and PRKO-S+PRKO-E tissue recombinants, Thus, both epithelial and strom al PR are essential for full P-4 inhibition of E-2-induced lactoferrin expr ession.