The in vivo role of glucocorticoids in controlling prostaglandin endoperoxide 
synthase-2 (PTGS2) expression in the human amnion is unclear despite extensive 
studies using in vitro models. We addressed this issue by determining PTGS2 mRNA 
levels and gene transcriptional activity, RNA polymerase-II (pol-II) binding, 
pol-II C-terminal domain (CTD) phosphorylation, histone acetylation, and histone 
methylation at the PTGS2 gene in fresh amnion and in amnion explants incubated 
with dexamethasone for 24 h after delivery, when adaptation from in vivo to in 
vitro conditions occurred. PTGS2 mRNA turnover changed during incubation 
involving the initial rapid decrease and subsequent rebound of the transcription 
rate and stabilization of mRNA. pol-II accumulated in the 5'-region of the gene, 
which indicated postinitiation pausing. pol-II binding, 5'-accumulation, 
C-terminal domain Ser-5 and Ser-2 phosphorylation, and histone acetylation 
decreased rapidly and did not reverse during the transcriptional rebound, 
suggesting that the transcriptional mechanism altered in vitro. Dexamethasone 
decreased PTGS2 gene activity and mRNA levels. Glucocorticoid receptor-α (GRα) 
was bound to the PTGS2 promoter but did not affect pol-II recruitment, pausing, 
or the epigenetic marks. GRα binding, however, decreased initiating (Ser-5) and 
elongating (Ser-2) pol-II phosphorylation. The ability of the PTGS2 promoter to 
bind GRα in response to dexamethasone diminished during incubation. We conclude 
that PTGS2 mRNA turnover is accelerated in vivo, but the underlying mechanisms 
are not sustained beyond 24 h in explants. Glucocorticoids chronically 
transrepress PTGS2 gene activity in vivo in part by interfering with 
transcription initiation and elongation. Glucocorticoid transrepression of PTGS2 
may be important for pregnancy maintenance and the timing of parturition.