Regulation of prostaglandin H synthase-2 in chorion and decidual cells

The regulation of chorio-decidual prostaglandin biosynthesis has important implications for our understanding of the mechanisms of human parturition. It has been known for many years that prostaglandin H synthase (PGHS) is a key enzyme in prostaglandin biosynthesis but recently an inducible form (PGHS-2) has been identified that is separate from the constitutive form (PGHS-1). We have evaluated whether substances known to stimulate prostaglandin biosynthesis in chorio-decidua act via PGHS-2. Human chorion and decidual cells were grown to confluence and treated for up to 16 h with interleukin 1 beta 10 ng/ml), epidermal growth factor (EGF) (10 ng/ml) or phorbol 12-myristate 13-acetate (PMA) (10(-7) M). Microsomal protein was isolated, separated by gel electrophoresis and PGHS-2 amounts determined using an antibody specific for PGHS-2. All three test agents caused an increase in PGHS-2 levels in chorion cells (189%-288%) and decidual cells (153%-541%). Hence, induction of PGHS-2 is one of the mechanisms by which several substances can elevate the rate of prostaglandin biosynthesis.