Modulation of progesterone receptor isoform expression in pregnant human myometrium

Background: Regulation of myometrial progesterone receptor (PR) expression is an unresolved issue central to understanding the mechanism of functional progesterone withdrawal and initiation of labor in women. Objectives: To determine whether pregnant human myometrium undergoes culture-induced changes in <i>PR</i> isoform expression ex situ and, further, to determine if conditions approaching the in vivo environment stabilise <i>PR</i> isoform expression in culture. Methods: Term nonlaboring human myometrial tissues were cultured under specific conditions: serum supplementation, steroids, stretch, cAMP, PMA, PGF_2α, NF-κB inhibitors, or TSA. Following 48 h culture, <i>PR-T, PR-A,</i> and <i>PR-B</i> mRNA levels were determined using qRT-PCR. <i>PR-A/PR-B</i> ratios were calculated. Results: <i>PR-T</i> and <i>PR-A</i> expression and the <i>PR-A/PR-B</i> ratio significantly increased in culture. Steroids prevented the culture-induced increase in <i>PR-T</i> and <i>PR-A</i> expression. Stretch blocked the effects of steroids on <i>PR-T</i> and <i>PR-A</i> expression. PMA further increased the <i>PR-A/PR-B</i> ratio, while TSA blocked culture-induced increases of <i>PR-A</i> expression and the <i>PR-A/PR-B</i> ratio. Conclusion: Human myometrial tissue in culture undergoes changes in <i>PR</i> gene expression consistent with transition toward a laboring phenotype. TSA maintained the nonlaboring PR isoform expression pattern. This suggests that preserving histone and/or nonhistone protein acetylation is critical for maintaining the progesterone dependent quiescent phenotype of human myometrium in culture.