Regulation of the progesterone receptor and estrogen receptor in decidua basalis by progesterone and estradiol during pregnancy

In this study we examined the roles of progesterone (P-4) and estradiol-17 beta (E-2) in regulation of the P-4 receptor (PR) and estrogen receptor (ER) in the decidua basalis (DB) during stromal cell proliferation and regression (Days 10 and 14 of pregnancy, respectively). Pregnant rats were ovariectomized (Ovx) on Day 8 or 12 and killed on Day 10 or 14, respectively, following treatment with P-4, E-2, or both. In some experiments, rats received pellets of the anti-progestin RU-486 on Day 9 and were killed 3, 6, 12, and 24 h later. Immunolocalization of PR and ER showed that both receptors decreased from Day 10 to Day 14. Histologic integrity of the placenta and DB were maintained only when P-4 was present. Control and hormone-treated groups expressed established isoforms of PR and ER: PR-B, 110 kDa; PR-A, 80-90 kDa; PR-C, 64-60 kDa; ER-66, 66 kDa; and ER-49, 49 kDa. On Day 10, expression of PR-A, PR-B, and ER-66 decreased 50-99% (p < 0.05) after Ovx or RU-486 treatment but was restored to control levels after Ovx by exogenous P-4. On Day 14, PR-B and ER-66 declined 66-75% (p < 0.05) after Ovx and could not be restored by P-4 treatment. Estrogen could not substitute for P-4, and co-administration of E-2 with P-4 did not enhance the response over P-4 alone. In contrast, PR-C was abundantly expressed on Days 10 and 14 in all treatment groups after Ovx and RU-486. P-4 maintained PR mRNA and ER mRNA after Ovx. Thus, regression of the DB may be initiated via changes in relative expression of PR isoforms, which result in impaired stromal cell response to P-4 action.