Regulation of the two prostaglandin G/H synthases by parathyroid hormone, interleukin-1, cortisol, and prostaglandin E2 in cultured neonatal mouse calvariae.
A second prostaglandin G/H synthase (PGHS-2), encoded by a gene separate from that for the original PGHS (PGHS-1), has recently been identified. We have shown that PGHS-2 is expressed in cultured mouse calvariae and have compared regulation of PGHS-2 and PGHS-1 messenger RNA (mRNA) levels. PGHS-2 mRNA was not detectable in freshly isolated bones, but was induced during culture and further stimulated by interleukin-1 (IL-1) and PTH. Both factors also increased PGHS-2 protein levels. Changes in medium prostaglandin E2 (PGE2) production correlated with increases in PGHS-2 mRNA levels. However, with IL-1, PGE2 production was increased more than PGHS-2 mRNA levels (treated/control ratio, 3.4 and 1.5, respectively), whereas with PTH there was a closer correspondence (2.0 and 2.1). Cortisol reduced PTH-stimulated PGE2 production (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 acid, changes in PGHS-2 mRNA levels with IL-1, PTH, and cortisol correlated closely with changes in PGE2 production. PGE2 itself increased PGHS-2 mRNA, and nonsteroidal antiinflammatory drugs decreased PGHS-2 mRNA levels by 80%. In contrast, PGHS-1 mRNA was expressed constitutively and was not affected by IL-1, PTH, or cortisol when measured by competitive reverse transcriptase-polymerase chain reaction. We conclude that regulation of PGE2 production is predominantly through PGHS-2, rather than PGHS-1; that IL-1 and cortisol may also regulate arachidonic acid release; and that PGE2 may amplify its own production through stimulation of PGHS-2.
Kawaguchi
H
H
Department of Medicine, University of Connecticut Health Center, Farmington 06030.
Raisz
L G
LG
Voznesensky
O S
OS
Alander
C B
CB
Hakeda
Y
Y
Pilbeam
C C
CC
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D046508:Culture Techniques; D015232:Dinoprostone / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012886:Skull / Q000201:enzymology*; D014158:Transcription, Genetic
D007375:Interleukin-1; D015335:Molecular Probes; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D006854:Hydrocortisone