Endocrinology, Vol 137, 5435-5440, Copyright © 1996 by Endocrine Society

ARTICLES

Parathyroid hormone induces prostaglandin G/H synthase-2 expression by a cyclic adenosine 3',5'-monophosphate-mediated pathway in the murine osteoblastic cell line MC3T3-E1

S Tetradis, CC Pilbeam, Y Liu and BE Kream
Department of Oral Diagnosis, School of Dental Medicine, University of Connecticut Health Center, Farmington 06030, USA.

Prostaglandin G/H synthase (PGHS), a central enzyme for PG synthesis, is encoded by the constitutively expressed PGHS-1 and the inducible PGHS-2. The goal of this project was to study the regulation of PGHS-2 gene expression by PTH and its possible signaling pathways in osteoblastic MC3T3-E1 cultures. Bovine PTH-(1-34) at 0.01-10 nM increased PGHS-2, but not PGHS-1, messenger RNA (mRNA) levels. The effect of PTH was maximal at 1 h and decreased almost to control levels by 6 h. Phorbol myristate acetate (PMA), forskolin, and 8-bromo-cAMP increased PGHS-2 mRNA levels, whereas ionomycin had no effect. PTH, forskolin, and PMA increased the release of PGE2 into the culture medium. Pretreatment of cells with 0.1 microM PMA for 16 h blocked the induction of PGHS-2 mRNA levels by PMA, but did not alter the effects of PTH and forskolin. However, treatment of cells with 30 microM H-89, a protein kinase A inhibitor, significantly reduced the ability of PTH and forskolin to induce PGHS-2 mRNA levels. Moreover, PTH-(3-34) at 0.1- 100 nM did not induce PGHS-2 mRNA levels. Our results show that PTH can rapidly and transiently induce PGHS-2 mRNA levels in osteoblastic MC3T3- E1 cells, primarily via the cAMP-protein kinase A signal transduction pathway. Induction of PGHS-2 may play a key role in mediating some actions of PTH on bone metabolism and gene expression.

This article has been cited by other articles:

				M. Huening, G. Yehia, C. A. Molina, and S. Christakos Evidence for a Regulatory Role of Inducible cAMP Early Repressor in Protein Kinase A-Mediated Enhancement of Vitamin D Receptor Expression and Modulation of Hormone Action Mol. Endocrinol., September 1, 2002; 16(9): 2052 - 2064. [Abstract] [Full Text] [PDF]

				S. Tetradis, O. Bezouglaia, and A. Tsingotjidou Parathyroid Hormone Induces Expression of the Nuclear Orphan Receptor Nurr1 in Bone Cells Endocrinology, February 1, 2001; 142(2): 663 - 670. [Abstract] [Full Text] [PDF]

				R. R. Miles, J. P. Sluka, D. L. Halladay, R. F. Santerre, L. V. Hale, L. Bloem, K. Thirunavukkarasu, R. J. S. Galvin, J. M. Hock, and J. E. Onyia ADAMTS-1: A Cellular Disintegrin and Metalloprotease with Thrombospondin Motifs Is a Target for Parathyroid Hormone in Bone Endocrinology, December 1, 2000; 141(12): 4533 - 4542. [Abstract] [Full Text] [PDF]

				N. S. Krieger, W. R. Parker, K. M. Alexander, and D. A. Bushinsky Prostaglandins regulate acid-induced cell-mediated bone resorption Am J Physiol Renal Physiol, December 1, 2000; 279(6): F1077 - F1082. [Abstract] [Full Text] [PDF]

				N. Selvamurugan, M. R. Pulumati, D. R. Tyson, and N. C. Partridge Parathyroid Hormone Regulation of the Rat Collagenase-3 Promoter by Protein Kinase A-dependent Transactivation of Core Binding Factor alpha 1 J. Biol. Chem., February 18, 2000; 275(7): 5037 - 5042. [Abstract] [Full Text] [PDF]

				C. Pilbeam, Y. Rao, O. Voznesensky, H. Kawaguchi, C. Alander, L. Raisz, and H. Herschman Transforming Growth Factor-{beta}1 Regulation of Prostaglandin G/H Synthase-2 Expression in Osteoblastic MC3T3-E1 Cells Endocrinology, November 1, 1997; 138(11): 4672 - 4682. [Abstract] [Full Text] [PDF]

				S. Tetradis, C. C. Pilbeam, Y. Liu, H. R. Herschman, and B. E. Kream Parathyroid Hormone Increases Prostaglandin G/H Synthase-2 Transcription by a Cyclic Adenosine 3',5'-Monophosphate-Mediated Pathway in Murine Osteoblastic MC3T3-E1 Cells Endocrinology, September 1, 1997; 138(9): 3594 - 3600. [Abstract] [Full Text] [PDF]

				D. A. Bushinsky, W. R. Parker, K. M. Alexander, and N. S. Krieger Metabolic, but not respiratory, acidosis increases bone PGE2 levels and calcium release Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1058 - F1066. [Abstract] [Full Text] [PDF]