Journal
BIOLOGY OF REPRODUCTION
Volume 64, Issue 1, Pages 272-283Publisher
OXFORD UNIV PRESS INC
DOI: 10.1095/biolreprod64.1.272
Keywords
decidua; estradiol; progesterone receptor; uterus
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Funding
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK047517] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG015500, R01AG013784] Funding Source: NIH RePORTER
- NIA NIH HHS [AG-15500, AG-13784] Funding Source: Medline
- NIDDK NIH HHS [DK47517] Funding Source: Medline
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Regulation of progesterone receptor (PR) in uterine stroma (endometrial stroma plus myometrium) by estrogen was investigated in estrogen receptor-alpha (ER alpha) knockout (alpha ERKO) mice. 17 beta -Estradiol (E-2) increased PR levels in uterine stroma of ovariectomized alpha ERKO mice, and ICI 182 780 (ICI) inhibited this E-2-induced PR expression. Estrogen receptor-beta (ERP) was detected in both uterine epithelium and stroma of wild-type and alpha ERKO mice by immunohistochemistry. In organ cultures of alpha ERKO uterus, both E-2 and diethylstilbestrol induced stromal PR, and ICI inhibited this induction. These findings suggest that estrogen induces stromal PR via ER beta in alpha ERKO uterus. However, this process is not mediated exclusively by ER beta, because in ER beta knockout mice, which express ER alpha, PR was up-regulated by E-2 in uterine stroma. In both wild-type and alpha ERKO mice, progesterone and mechanical traumatization were essential and sufficient to induce decidual cells, even though E-2 and ER alpha were also required for increase in uterine weight. Progesterone receptor was strongly expressed in decidual cells in alpha ERKO mice, and ICI did not inhibit decidualization or PR expression. This study suggests that up-regulation of PR in endometrial stroma is mediated through at least three mechanisms: 1) classical estrogen signaling through ER alpha, 2) estrogen signaling through ER beta, and 3) as a result of mechanical stimulation plus progesterone, which induces stromal cells to differentiate into decidual cells. Each of these pathways can function independently of the others.
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