This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Patel, F. A. Articles by Challis, J. R. G. Search for Related Content PubMed PubMed Citation Articles by Patel, F. A. Articles by Challis, J. R. G.

Steroid Regulation of Prostaglandin Dehydrogenase Activity and Expression in Human Term Placenta and Chorio-Decidua in Relation to Labor¹

Medical Research Council Group in Fetal and Neonatal Health and Development, Departments of Physiology and Obstetrics and Gynecology (F.A.P, V.L.C., J.R.G.C.), University of Toronto, Toronto, Ontario, Canada; and Research Laboratories of Schering AG (K.C.), Berlin, Germany

Address all correspondence and requests for reprints to: Dr. Falguni A. Patel, 1 Kings College Circle, Medical Sciences Building, Room 3209, Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8. E-mail: fal.patel{at}utoronto.ca

NAD⁺-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) is the key catabolic enzyme controlling levels of biologically active PGs. PGDH is localized to syncytiotrophoblast in placenta, and to trophoblast cells in chorion. To examine the regulation of PGDH by steroids and to determine any changes with labor, we obtained placenta and chorion from term elective cesarean section or spontaneous delivery and isolated trophoblast cells using a Percoll density gradient. Cells were treated with varying concentrations of cortisol, progesterone, the synthetic progestins R5020, and medroxyprogesterone acetate with or without RU486 or the specific progesterone receptor antagonist, onapristone, and the 3ß-hydroxysteroid dehydrogenase inhibitor, trilostane. The activity of PGDH was assessed by measurement of 13,14-dihydro-15-keto-PGF₂. PGDH messenger ribonucleic acid was quantified by in situ hybridization and computerized image analysis.

The basal output of 13,14-dihydro-15-keto-PGF₂ was lower in placenta or chorion collected at spontaneous labor than in that obtained at elective cesarean section. Cortisol had a significant dose-dependent inhibitory effect on PGDH activity in both placental and chorion trophoblast cells and significantly decreased levels of PGDH messenger ribonucleic acid. Responses were similar between tissues from laboring and nonlaboring women. PGDH activity was increased by R5020 and medroxyprogesterone acetate and was inhibited by RU486, onapristone, and trilostane. We conclude that cortisol inhibits PGDH activity and expression and that progestagens increase PGDH activity in human chorion and placenta.

This article has been cited by other articles:

				A. E. Michael and A. T. Papageorghiou Potential significance of physiological and pharmacological glucocorticoids in early pregnancy Hum. Reprod. Update, September 1, 2008; 14(5): 497 - 517. [Abstract] [Full Text] [PDF]

				H. Chisaka, J. F. Johnstone, M. Premyslova, Z. Manduch, and J. R.G. Challis Effect of Pro-inflammatory Cytokines on Expression and Activity of 11{beta}-Hydroxysteroid Dehydrogenase Type 2 in Cultured Human Term Placental Trophoblast and Human Choriocarcinoma JEG-3 Cells Reproductive Sciences, July 1, 2005; 12(5): 303 - 309. [Abstract] [PDF]

				J. F. Johnstone, A. D. Bocking, E. Unlugedik, and J. R.G. Challis The Effects of Chorioamnionitis and Betamethasone on 11{beta}, Hydroxysteroid Dehydrogenase Types 1 and 2 and the Glucocorticoid Receptor in Preterm Human Placenta Reproductive Sciences, May 1, 2005; 12(4): 238 - 245. [Abstract] [PDF]

				R. F. Johnson, C. M. Mitchell, V. Clifton, and T. Zakar Regulation of 15-Hydroxyprostaglandin Dehydrogenase (PGDH) Gene Activity, Messenger Ribonucleic Acid Processing, and Protein Abundance in the Human Chorion in Late Gestation and Labor J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5639 - 5648. [Abstract] [Full Text] [PDF]

				M. Lappas, M. Permezel, H. M. Georgiou, and G. E. Rice Regulation of Phospholipase Isozymes by Nuclear Factor-{kappa}B in Human Gestational Tissues in Vitro J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2365 - 2372. [Abstract] [Full Text] [PDF]

				N. Mirazi, N. Alfaidy, R. Martin, and J. R. G. Challis Effects of Dexamethasone and Sulfasalazine on Prostaglandin E2 Output by Human Placental Cells In Vitro Reproductive Sciences, January 1, 2004; 11(1): 22 - 26. [Abstract] [PDF]

				N. Alfaidy, W. Li, T. MacIntosh, K. Yang, and J. Challis Late Gestation Increase in 11{beta}-Hydroxysteroid Dehydrogenase 1 Expression in Human Fetal Membranes: A Novel Intrauterine Source of Cortisol J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 5033 - 5038. [Abstract] [Full Text] [PDF]

				F. A. Patel, J. W. Funder, and J. R. G. Challis Mechanism of Cortisol/Progesterone Antagonism in the Regulation of 15-Hydroxyprostaglandin Dehydrogenase Activity and Messenger Ribonucleic Acid Levels in Human Chorion and Placental Trophoblast Cells at Term J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2922 - 2933. [Abstract] [Full Text] [PDF]

				K. J. McKeown and J. R. G. Challis Regulation of 15-Hydroxy Prostaglandin Dehydrogenase by Corticotrophin-Releasing Hormone through a Calcium-Dependent Pathway in Human Chorion Trophoblast Cells J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1737 - 1741. [Abstract] [Full Text] [PDF]

				A. I. Ivanov, A. C. Scheck, and A. A. Romanovsky Expression of genes controlling transport and catabolism of prostaglandin E2 in lipopolysaccharide fever Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2003; 284(3): R698 - R706. [Abstract] [Full Text] [PDF]

				E. Hirsch and R. Muhle Intrauterine Bacterial Inoculation Induces Labor in the Mouse by Mechanisms Other than Progesterone Withdrawal Biol Reprod, October 1, 2002; 67(4): 1337 - 1341. [Abstract] [Full Text] [PDF]

				D. Giannoulias, F. A. Patel, A. C. Holloway, S. J. Lye, H. H. Tai, and J. R. G. Challis Differential Changes in 15-Hydroxyprostaglandin Dehydrogenase and Prostaglandin H Synthase (Types I and II) in Human Pregnant Myometrium J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1345 - 1352. [Abstract] [Full Text] [PDF]

				F. A. Patel and J. R. G. Challis Cortisol/Progesterone Antagonism in Regulation of 15-Hydroxysteroid Dehydrogenase Activity and mRNA Levels in Human Chorion and Placental Trophoblast Cells at Term J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 700 - 708. [Abstract] [Full Text] [PDF]

				N. Alfaidy, Z. G. Xiong, L. Myatt, Stephen. J. Lye, J. F. MacDonald, and J. R. G. Challis Prostaglandin F2{alpha} Potentiates Cortisol Production by Stimulating 11{beta}-Hydroxysteroid Dehydrogenase 1: A Novel Feedback Loop That May Contribute to Human Labor J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5585 - 5592. [Abstract] [Full Text] [PDF]

				W.L. Whittle, F.A. Patel, N. Alfaidy, A.C. Holloway, M. Fraser, S. Gyomorey, S.J. Lye, W. Gibb, and J.R.G. Challis Glucocorticoid Regulation of Human and Ovine Parturition: The Relationship Between Fetal Hypothalamic-Pituitary-Adrenal Axis Activation and Intrauterine Prostaglandin Production Biol Reprod, April 1, 2001; 64(4): 1019 - 1032. [Abstract] [Full Text]

				E. Schoof, M. Girstl, W. Frobenius, M. Kirschbaum, H. G. Dörr, W. Rascher, and J. Dötsch Decreased Gene Expression of 11{beta}-Hydroxysteroid Dehydrogenase Type 2 and 15-Hydroxyprostaglandin Dehydrogenase in Human Placenta of Patients with Preeclampsia J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1313 - 1317. [Abstract] [Full Text]

				J. R.G. Challis, S. G. Matthews, W. Gibb, and S. J. Lye Endocrine and Paracrine Regulation of Birth at Term and Preterm Endocr. Rev., October 1, 2000; 21(5): 514 - 550. [Abstract] [Full Text]

				W. L. Whittle, A. C. Holloway, S. J. Lye, W. Gibb, and J. R. G. Challis Prostaglandin Production at the Onset of Ovine Parturition Is Regulated by Both Estrogen-Independent and Estrogen-Dependent Pathways Endocrinology, October 1, 2000; 141(10): 3783 - 3791. [Abstract] [Full Text] [PDF]

				W. X. Wu, X. H. Ma, G. C. S. Smith, C. A. Mecenas, S. V. Koenen, and P. W. Nathanielsz Prostaglandin dehydrogenase mRNA in baboon intrauterine tissues in late gestation and spontaneous labor Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2000; 279(3): R1082 - R1090. [Abstract] [Full Text] [PDF]

				F. C. Denison, S. C. Riley, C. L. Elliott, R. W. Kelly, A. A. Calder, and H. O.D. Critchley The effect of mifepristone administration on leukocyte populations, matrix metalloproteinases and inflammatory mediators in the first trimester cervix Mol. Hum. Reprod., June 1, 2000; 6(6): 541 - 548. [Abstract] [Full Text] [PDF]

				N. Hanna, I. Hanna, M. Hleb, E. Wagner, J. Dougherty, D. Balkundi, J. Padbury, and S. Sharma Gestational Age-Dependent Expression of IL-10 and Its Receptor in Human Placental Tissues and Isolated Cytotrophoblasts J. Immunol., June 1, 2000; 164(11): 5721 - 5728. [Abstract] [Full Text] [PDF]

				K. J. Greenland, I. Jantke, S. Jenatschke, K. E. Bracken, C. Vinson, and B. Gellersen The Human NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase Gene Promoter Is Controlled by Ets and Activating Protein-1 Transcription Factors and Progesterone Endocrinology, February 1, 2000; 141(2): 581 - 597. [Abstract] [Full Text] [PDF]

				Interleukin-10 Modifies the Effects of Interleukin-1{beta} and Tumor Necrosis Factor-{alpha} on the Activity and Expression of Prostaglandin H Synthase-2 and the NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase in Cultured Term Human Villous Trophoblast and Chorion Trophoblast Cells J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4645 - 4651. [Abstract] [Full Text]

				F. A. Patel, K. Sun, and J. R. G. Challis Local Modulation by 11{beta}-Hydroxysteroid Dehydrogenase of Glucocorticoid Effects on the Activity of 15-Hydroxyprostaglandin Dehydrogenase in Human Chorion and Placental Trophoblast Cells J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 395 - 400. [Abstract] [Full Text]