Glucocorticoids stimulate prostaglandin H synthase type-2 (PGHS-2) in the fibroblast cells in human amnion cultures.
The human amnion may be an important source of prostaglandins involved in the onset of labour. Glucocorticoids are possible regulators of amnion prostaglandin synthesis and have been shown to stimulate the PGE2 output and prostaglandin H2 synthase (PGHS) activity of human amnion cells maintained in primary monolayer culture. There are two known isoforms of PGHS: the constitutively expressed PGHS-1 and the inducible PGHS-2. Recent studies have shown that the latter isoform is induced by glucocorticoids. The amnion consists of a single layer of epithelial cells beneath which lies a mesenchymal layer containing fibroblasts and it is not known which cell types are responding to glucocorticoids in this manner. In the present study, we demonstrate that although both cell types are present in culture, PGHS-2 protein and mRNA levels increase exclusively within the fibroblasts in response to dexamethasone, while PGHS-1 protein and mRNA levels remain unaffected in both cell types. These results suggest that the stimulation of PGE2 in cultured amnion cells by glucocorticoids is due to an upregulation of PGHS-2 gene transcription in fibroblasts, and that these previously overlooked cells may have important roles to play in the synthesis of prostaglandins involved in labour.
Economopoulos
P
P
Department of Obstetrics and Gynecology and Physiology, University of Ottawa, Ottawa General Hospital, Ontario, Canada.
Sun
M
M
Purgina
B
B
Gibb
W
W
D000650:Amnion / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D005938:Glucocorticoids; D007527:Isoenzymes; D012333:RNA, Messenger; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases