Prostaglandin G/H Synthase (PGHS)-2 Expression in Bovine Myometrium: Influence of Steroid Hormones and PGHS Inhibitors(2)

19 Feb
2013

Prostaglandin G/H synthase (PGHS) and phospholipase A2 (PLA2) are the key enzymes in the release and conversion of arachidonic acid (AA) to PGH2 that is subsequently converted to PGD2, PGE2, PGF2a, PGI2, and thromboxane A2 by specific synthases. Two PGHS isoforms are encoded by two different genes; the constitutive form (PGHS-1) is assumed to be involved in producing prostanoids for cellular ‘‘housekeeping’’ functions whereas the newly described inducible form (PGHS-2) is expressed under specific conditions in cells and strongly down-regulated by glucocorticoids. Although PGHS-1 and PGHS-2 enzymes share a high degree of homology (60-70%), several studies using available nonsteroidal anti-inflammatory drugs have demonstrated that the two isoforms can be inhibited differentially.

Evidence supporting the role of prostanoids in the control of uterine contractility has been reported. However, little is known about the fine mechanisms involved in the local changes affecting myometrial PG biosynthesis. The aim of the present study was to document the specific mechanisms regulating PG formation in bovine myometrium. We examined the differential expression of the PGHS (PGHS-1 and PGHS-2), cytosolic phospholipase A2 (cPLA2), and prostaglandin I2 synthase (PGI synthase) transcripts and/or their related gene products in the two myo-metrial layers. We concurrently investigated the effects of sex steroid hormones (estradiol-17p ± progesterone) and a specific PGHS-2 antagonist, CGP 28238 (Ciba-Geigy Healthcare Canada Ltd., Calgary, AB; 6-[2,4-difluorophenoxy]-5-methyl-sulfonylamino-1-indanone), on PG biosynthesis and PGHS-2 gene expression.

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