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 Schoof, E. Articles by Dötsch, J. Search for Related Content PubMed PubMed Citation Articles by Schoof, E. Articles by Dötsch, J.

Decreased Gene Expression of 11ß-Hydroxysteroid Dehydrogenase Type 2 and 15-Hydroxyprostaglandin Dehydrogenase in Human Placenta of Patients with Preeclampsia

Departments of Pediatrics (E.S., M.G., H.G.D., W.R., J.D.) and Obstetrics and Gynecology (W.F.), University of Erlangen-Nuremberg, 91054 Erlangen; and Department of Obstetrics and Gynecology, University of Giessen (M.K.), 35385 Giessen, Germany

Address all correspondence and requests for reprints to: Jörg Dötsch, M.D., Klinik für Kinder und Jugendliche, Friedrich-Alexander-Universität Erlangen-Nürnberg, Loschgestrasse 15, 91054 Erlangen, Germany. E-mail: joergwdoetsch{at}yahoo.com

Cortisol reduces the activity of the PG-inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) in human placental cells. The objective was to investigate a possible relation between 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), converting cortisol to cortisone, and PGDH gene expression in the placenta of patients with preeclampsia.

In placental tissue taken from 20 healthy women with normal pregnancy, 20 premature babies born after labor before term, and 18 neonates after preeclamptic pregnancy, 11ß-HSD2 and PGDH messenger RNA (mRNA) expression was determined using quantitative TaqMan real-time PCR and quantitative competitive PCR. When comparing matched pairs, there were 3-fold lower 11ß-HSD2/glyceraldehyde-3-phosphate dehydrogenase (11ß-HSD2/GAPDH) mRNA levels in placentas of patients with preeclampsia than in controls [0.18 ± 0.04 relative units (RU) and 0.61 ± 0.10 RU, P = 0.0003]. We also found a 2-fold reduction in placental PGDH/GAPDH mRNA concentrations (0.28 ± 0.15 RU and 0.50 ± 0.18 RU, P = 0.0003). PGDH and 11ß-HSD2 mRNA levels correlated significantly (r = 0.66, P < 0.0001). In term placenta, 11ß-HSD2/GAPDH, but not PGDH, showed a significant correlation to birth weight (r = 0.43, P = 0.01) and to placental weight (r = 0.47, P = 0.01). Results could be confirmed by competitive PCR.

We conclude that, in preeclampsia, 11ß-HSD2 mRNA expression is reduced, leading to the known decrease of 11ß-HSD2 activity. By means of an autocrine or paracrine mechanism, the diminished conversion of placental cortisol may lead to reduced PGDH mRNA expression as found in the present study.

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]

				T Dwyer, L Blizzard, B Patterson, A-L Ponsonby, K Martin, S Quinn, M M Sale, S M Richards, R Morley, S Rich, et al. Association between birth weight and adolescent systolic blood pressure in a caucasian birth cohort differs according to skin type, CRH promoter or 11{beta}-HSD2 genotype Arch. Dis. Child., September 1, 2008; 93(9): 760 - 767. [Abstract] [Full Text] [PDF]

				K. Matsushita, Y. Wu, Y. Okamoto, R. E. Pratt, and V. J. Dzau Local Renin Angiotensin Expression Regulates Human Mesenchymal Stem Cell Differentiation to Adipocytes Hypertension, December 1, 2006; 48(6): 1095 - 1102. [Abstract] [Full Text] [PDF]

				D. J. Powell Jr., M. E. Dudley, K. A. Hogan, J. R. Wunderlich, and S. A. Rosenberg Adoptive Transfer of Vaccine-Induced Peripheral Blood Mononuclear Cells to Patients with Metastatic Melanoma following Lymphodepletion J. Immunol., November 1, 2006; 177(9): 6527 - 6539. [Abstract] [Full Text] [PDF]

				V. E. Murphy, R. Smith, W. B. Giles, and V. L. Clifton Endocrine Regulation of Human Fetal Growth: The Role of the Mother, Placenta, and Fetus Endocr. Rev., April 1, 2006; 27(2): 141 - 169. [Abstract] [Full Text] [PDF]

				K. Yang, L. Julan, F. Rubio, A. Sharma, and H. Guan Cadmium reduces 11{beta}-hydroxysteroid dehydrogenase type 2 activity and expression in human placental trophoblast cells Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E135 - E142. [Abstract] [Full Text] [PDF]

				B. Kadereit, P. Fustier, K. Shojaati, B. M. Frey, F. J. Frey, and M. G. Mohaupt Extracellular ATP Determines 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Activity via Purinergic Receptors J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3507 - 3516. [Abstract] [Full Text] [PDF]

				M. Quinkler and P. M. Stewart Hypertension and the Cortisol-Cortisone Shuttle J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2384 - 2392. [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]

				S. Tenhola, E. Rahiala, A. Martikainen, P. Halonen, and R. Voutilainen Blood Pressure, Serum Lipids, Fasting Insulin, and Adrenal Hormones in 12-Year-Old Children Born with Maternal Preeclampsia J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1217 - 1222. [Abstract] [Full Text] [PDF]

				E. Kajantie, L. Dunkel, U. Turpeinen, U.-H. Stenman, P. J. Wood, M. Nuutila, and S. Andersson Placental 11{beta}-Hydroxysteroid Dehydrogenase-2 and Fetal Cortisol/Cortisone Shuttle in Small Preterm Infants J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 493 - 500. [Abstract] [Full Text] [PDF]

				D. B. Hardy and K. Yang The Expression of 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Is Induced during Trophoblast Differentiation: Effects of Hypoxia J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3696 - 3701. [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]