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

被引:92
作者
KAWAGUCHI, H
RAISZ, LG
VOZNESENSKY, OS
ALANDER, CB
HAKEDA, Y
PILBEAM, CC
机构
关键词
D O I
10.1210/en.135.3.1157
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 E(2) (PGE(2)) production correlated with increases in PGHS-(2) mRNA levels. However, with IL-1, PGE(2) 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 PGE(2) 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 PGE(2) production. PGE(2) 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 PGE(2) production is predominantly through PGHS-(2), rather than PGHS-1; that IL-1 and cortisol may also regulate arachidonic acid release; and that PGE(2) may amplify its own production through stimulation of PGHS-2.
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页码:1157 / 1164
页数:8
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