GLUCOCORTICOIDS STIMULATE PROSTAGLANDIN-H SYNTHASE TYPE-2 (PGHS-2) INTHE 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 am nion prostaglandin synthesis and have been shown to stimulate the PGE( 2) output and prostaglandin H-2 synthase (PGHS) activity of human amni on cells maintained in primary monolayer culture. There are two known isoforms of PGHS: the constitutively expressed PGHS-1 and the inducibl e PGHS-2. Recent studies have shown that the latter isoform is induced by glucocorticoids The amnion consists of a single layer of epithelia l 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 bo th cell types are present in culture, PGHS-2 protein and mRNA levels i ncrease exclusively within the fibroblasts in response to dexamethason e, while PGHS-1 protein and mRNA levels remain unaffected in both cell types. These results suggest that the stimulation of PGE(2) in cultur ed amnion cells by glucocorticoids is due to an upregulation of PGHS-2 gene transcription in fibroblasts, and that these previously overlook ed cells may have important roles to play in the synthesis of prostagl andins involved in labour.