help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Patel, F. A.
Right arrow Articles by Challis, J. R. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Patel, F. A.
Right arrow Articles by Challis, J. R. G.
The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 2 395-400
Copyright © 1999 by The Endocrine Society

Original Studies

Local Modulation by 11ß-Hydroxysteroid Dehydrogenase of Glucocorticoid Effects on the Activity of 15-Hydroxyprostaglandin Dehydrogenase in Human Chorion and Placental Trophoblast Cells1

Falguni A. Patel, Kang Sun and John R. G. Challis

University of Toronto, Departments of Physiology (F.A.P., K.S., J.R.G.C.) and Obstetrics and Gynaecology (J.R.G.C.), Medical Research Council Group in Fetal and Neonatal Health and Development (J.R.G.C.), Samuel Lunenfeld Research Institute, Mount Sinai Hospital (J.R.G.C.), Toronto, Canada

Address all correspondence and requests for reprints to: Ms. Fal Patel, Department of Physiology, 3rd Floor, Medical Sciences Building, University of Toronto, 1 King’s College Circle, Toronto, Ontario M5S 1A8, Canada. E-mail: fal.patel{at}utoronto.ca

NAD+-dependent 15-hydroxy-PG dehydrogenase (PGDH) is the major enzyme involved in the initial inactivation of PGs, and its activity is reduced by glucocorticoids, cortisol (F), and dexamethasone (DEX). In turn, glucocorticoid regulation of PGDH activity in placenta and chorion could be regulated indirectly by 11ß-hydroxysteroid dehydrogenase (11ß-HSD) activity. In the placenta, 11ß-HSD2 is the dominant isoform, acting as a dehydrogenase [F to cortisone (E)]; and in chorion, 11ß-HSD1 predominates as a reductase (E to F). The present study was designed to determine whether glucocorticoid regulation of PGDH activity in placenta and chorion could be regulated indirectly by 11ß-HSD activity. We obtained Percoll-purified human placental and chorion trophoblast cells from uncomplicated term pregnancies, cultured them for 72 h, then treated the cells with cortisol (100 nmol/L), cortisone (1 µmol/L), or DEX (100 nmol/L), in the presence or absence of carbenoxolone (CBX, 800 nmol/L), an 11ß-HSD inhibitor, for 24 h. Activity of PGDH was assessed by incubation (4 h) with PGF2{alpha} (282 nmol/L) and measurement of conversion to 13,14-dihydro-15-keto PGF2{alpha}. CBX alone had no effect on PGDH activity in either placenta or chorion trophoblast cells. In chorion, E significantly inhibited PGDH activity, and this effect was reversed by addition of CBX. F and DEX significantly inhibited PGDH, and this effect was unaltered by coadministration of CBX. In contrast, in placenta, there was no effect of E, or of E with CBX, on PGDH activity. However, F and DEX inhibited PGDH, and the effect of F (but not DEX) was greater in the presence of CBX. In conclusion, we suggest that effects of E and F on PGDH are modified by the tissue-specific expression of 11ß-HSD isoforms.




This article has been cited by other articles:


Home page
 Hum Reprod UpdateHome page
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]

Home page
 Mol. Endocrinol.Home page
X. Hu and J. W. Funder
The Evolution of Mineralocorticoid Receptors
Mol. Endocrinol., July 1, 2006; 20(7): 1471 - 1478.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
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]

Home page
 Reproductive SciencesHome page
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]

Home page
 Mol Hum ReprodHome page
P.M. Driver, S. Rauz, E.A. Walker, M. Hewison, M.D. Kilby, and P.M. Stewart
Characterization of human trophoblast as a mineralocorticoid target tissue
Mol. Hum. Reprod., December 1, 2003; 9(12): 793 - 798.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Suzuki, K. Koyama, A. Darnel, H. Ishibashi, S. Kobayashi, H. Kubo, T. Suzuki, H. Sasano, and Z. S. Krozowski
Dexamethasone Upregulates 11{beta}-Hydroxysteroid Dehydrogenase Type 2 in BEAS-2B Cells
Am. J. Respir. Crit. Care Med., May 1, 2003; 167(9): 1244 - 1249.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
S. Gupta, S. Gyomorey, S. J. Lye, W. Gibb, and J. R. G. Challis
Effect of Labor on Glucocorticoid Receptor (GRTotal, GR{alpha}, and GR{beta}) Proteins in Ovine Intrauterine Tissues
Reproductive Sciences, April 1, 2003; 10(3): 136 - 144.
[Abstract] [PDF]

Home page
 Biol. Reprod.Home page
K. Sun, P. He, and K. Yang
Intracrine Induction of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression by Glucocorticoid Potentiates Prostaglandin Production in the Human Chorionic Trophoblast
Biol Reprod, November 1, 2002; 67(5): 1450 - 1455.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 Mol Hum ReprodHome page
P.M. Driver, M.D. Kilby, I. Bujalska, E.A. Walker, M. Hewison, and P.M. Stewart
Expression of 11{beta}-hydroxysteroid dehydrogenase isozymes and corticosteroid hormone receptors in primary cultures of human trophoblast and placental bed biopsies
Mol. Hum. Reprod., April 1, 2001; 7(4): 357 - 363.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
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]

Home page
 Biol. Reprod.Home page
Y. Ma, C. J. Lockwood, A. L. Bunim, D. A. Giussani, P. W. Nathanielsz, and S. Guller
Cell Type-Specific Regulation of Fetal Fibronectin Expression in Amnion: Conservation of Glucocorticoid Responsiveness in Human and Nonhuman Primates
Biol Reprod, June 1, 2000; 62(6): 1812 - 1817.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. Hirasawa, J. Takeyama, H. Sasano, K. Fukushima, T. Suzuki, Y. Muramatu, A. D. Darnel, C. Kaneko, N. Hiwatashi, T. Toyota, et al.
11{beta}-Hydroxysteroid Dehydrogenase Type II and Mineralocorticoid Receptor in Human Placenta
J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1306 - 1309.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. W. Funder
Editorial: 15-Hydroxyprostaglandin Dehydrogenase: Cinderella Meets Prince Serendip
J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 393 - 394.
[Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1999 by The Endocrine Society