REGULATION OF THE 2 PROSTAGLANDIN G H SYNTHASES BY PARATHYROID-HORMONE, INTERLEUKIN-1, CORTISOL, AND PROSTAGLANDIN E(2) IN CULTURED NEONATAL MOUSE CALVARIAE/

A second prostaglandin G/H synthase (PGHS-2), encoded by a gene separa te from that for the original PGHS (PGHS-1), has recently been identif ied. We have shown that PGHS-2 is expressed in cultured mouse calvaria e and have compared regulation of PGHS-2 and PGHS-1 messenger RNA (mRN A) levels. PGHS-2 mRNA was not detectable in freshly isolated bones, b ut was induced during culture and further stimulated by interleukin-1 (IL-1) and PTH. Both factors also increased PGHS-2 protein levels. Cha nges in medium prostaglandin E(2) (PGE(2)) production correlated with increases in PGHS-(2) mRNA levels. However, with IL-1, PGE(2) producti on was increased more than PGHS-2 mRNA levels (treated/control ratio, 3.4 and 1.5, -respectively), whereas with PTH there was a closer corre spondence (2.0 and 2.1). Cortisol reduced PTH-stimulated PGE(2) produc tion (treated/control ratio decreased from 3.1 to 0.2) more than PGHS- 2 mRNA levels (2.8 to 0.8). In the presence of exogenous arachidonic a cid, changes in PGHS-2 mRNA levels with IL-1, PTH, and cortisol correl ated closely with changes in PGE(2) production. PGE(2) itself increase d PGHS-2 mRNA, and nonsteroidal antiinflammatory drugs decreased PGHS- 2 mRNA levels by 80%. In contrast, PGHS-1 mRNA was expressed constitut ively and was not affected by IL-1, PTH, or cortisol when measured by competitive reverse transcriptase-polymerase chain reaction. We conclu de that regulation of PGE(2) production is predominantly through PGHS- (2), rather than PGHS-1; that IL-1 and cortisol may also regulate arac hidonic acid release; and that PGE(2) may amplify its own production t hrough stimulation of PGHS-2.