Stromal cell progesterone and estrogen receptors during proliferation and regression of the decidua basalis in the pregnant rat

This study examines the distribution and abundance of progesterone receptors (PR) and estrogen receptors (ER) in the decidua basalis (DB) during proliferation (Days 8-12 of gestation) and regression (Days 14-21) in the rat. Stromal cells of the DB and metrial gland exhibited strong nuclear immunostaining for PR throughout gestation. Nuclear localization of ER was detectable only between Days 8-12. The heavily granulated natural killer cells were always negative for PR and ER. DB were dissected between Days 8 and 17 to measure progesterone (P-4)-binding sites and receptor proteins by Western blotting. The latter revealed four specific PR isoforms: B (110 kDa), Al (90 kDa), A2 (76-82 kDa), and C (60-64 kDa). Stromal cell nuclei contained more than 50% of P-4-binding sites during DB proliferation but less than 22% during regression (p < 0.05). PR-A and PR-B expression was greatest at proliferative stages (p < 0.05). PR-C increased in relative abundance during DB regression. Two ER isoforms of 66 kDa and 49 kDa were revealed. The 66-kDa ER, the most abundant form, was maximally expressed during proliferation, declining 71% by Day 12 (p < 0.01), whereas the 49-kDa form accounted for up to 90% of ER during regression. Northern blot analysis revealed three prominent transcripts of approximately 11, 7, and 4 kilobases (kb) for PR mRNA, which declined markedly at Days 14 to 17 (p < 0.05), and one of 6.0 kb for ER mRNA, which declined markedly on Day 17 (p < 0.05). Our study establishes that the DB expresses heterogeneity of receptor message and proteins. We propose that preferential expression of receptor isoforms in late pregnancy limits P-4 action and promotes DB regression in spite of invariant levels of serum P-4, P-4-binding sites, and total receptor protein.