Molecular Human Reproduction, Vol. 7, No. 4, 357-363,
April 2001
© 2001 European Society of Human Reproduction and Embryology
Expression of 11ß-hydroxysteroid dehydrogenase isozymes and corticosteroid hormone receptors in primary cultures of human trophoblast and placental bed biopsies
Divisions of Medical Sciences and Reproductive and Child Health, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK
Interconversion of active and inactive glucocorticoids, e.g. cortisol (F) and cortisone (E) is catalysed by 11ß-hydroxysteroid dehydrogenase (11ß-HSD) which exists as two isoforms. We have used human placental bed biopsies and an in-vitro cytotrophoblast cell culture system to examine the expression and activity of the 11ß-HSD isoforms along with that of the glucocorticoid and mineralocorticoid receptors (GR and MR). Immunohistochemistry localized 11ß-HSD1 to decidualized stromal cells and 11ß-HSD2 to villous cytotrophoblast, syncytiotrophoblasts and trophoblast cells invading the placental bed and maternal vasculature. In primary cultures of human cytotrophoblast, 11ß-HSD2, GR and MR mRNA were expressed. Low levels of 11ß-HSD1 mRNA were noted in these cultured cells, but could be explained on the basis of contaminating, vimentin-positive decidual stromal cells (
5%). Enzyme activity studies confirmed the presence of a high-affinity, NAD-dependent dehydrogenase activity (Km 137 nmol/l and Vmax 128 pmol E/h/mg protein), indicative of the 11ß-HSD2 isoform. No reductase activity was observed. The presence of functional MR and GR was determined using Scatchard analyses of dexamethasone and aldosterone binding (MR Kd 1.4 nmol/l Bmax 3.0; GR Kd 6.6 nmol/l Bmax 16.2 fmol/ng protein). The expression of 11ß-HSD1 in maternal decidua and 11ß-HSD2 in adjacent trophoblast suggests an important role for glucocorticoids in determining trophoblast invasion. The presence of the MR within trophoblast indicates that some of the effects of cortisol could be MRrather than GR-mediated.
11ß-hydroxysteroid dehydrogenase/glucocorticoid receptor/mineralocorticoid receptor/placenta/trophoblast
1 To whom correspondence should be addressed. E-mail: m.d.kilby{at}bham.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
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]
|
|
|
|
 |
|
 M Mandl, N Ghaffari-Tabrizi, J Haas, G Nohammer, and G Desoye Differential glucocorticoid effects on proliferation and invasion of human trophoblast cell lines Reproduction, July 1, 2006; 132(1): 159 - 167. [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]
|
|
|
|
 |
|
 M.-J. Lee, Z. Wang, H. Yee, Y. Ma, N. Swenson, L. Yang, S. S. Kadner, R. N. Baergen, S. K. Logan, M. J. Garabedian, et al. Expression and Regulation of Glucocorticoid Receptor in Human Placental Villous Fibroblasts Endocrinology, November 1, 2005; 146(11): 4619 - 4626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Barber, J. A. Franklyn, C. J. McCabe, F. L. Khanim, J. N. Bulmer, G. S. J. Whitley, and M. D. Kilby The in Vitro Effects of Triiodothyronine on Epidermal Growth Factor-Induced Trophoblast Function J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1655 - 1661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Tomlinson, E. A. Walker, I. J. Bujalska, N. Draper, G. G. Lavery, M. S. Cooper, M. Hewison, and P. M. Stewart 11{beta}-Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response Endocr. Rev., October 1, 2004; 25(5): 831 - 866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. W. Chan, T. T. Lao, P. C. Ho, E. O. P. Sung, and A. N. Y. Cheung The Effect of Mifepristone on the Expression of Steroid Hormone Receptors in Human Decidua and Placenta: A Randomized Placebo-Controlled Double-Blind Study J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5846 - 5850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 H.G. Klemcke, R. Sampath Kumar, K. Yang, J.L. Vallet, and R.K. Christenson 11{beta}-Hydroxysteroid Dehydrogenase and Glucocorticoid Receptor Messenger RNA Expression in Porcine Placentae: Effects of Stage of Gestation, Breed, and Uterine Environment Biol Reprod, December 1, 2003; 69(6): 1945 - 1950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chan, S. Kachilele, E. Hobbs, J. N. Bulmer, K. Boelaert, C. J. McCabe, P. M. Driver, A. R. Bradwell, M. Kester, T. J. Visser, et al. Placental Iodothyronine Deiodinase Expression in Normal and Growth-Restricted Human Pregnancies J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4488 - 4495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhao, T. H. Kunz, N. Tumba, L. Clamon Schulz, C. Li, M. Reeves, and E. P. Widmaier Comparative analysis of expression and secretion of placental leptin in mammals Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R438 - R446. [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]
|
|
|
|
|
|
V. E. Murphy, T. Zakar, R. Smith, W. B. Giles, P. G. Gibson, and V. L. Clifton Reduced 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Activity Is Associated with Decreased Birth Weight Centile in Pregnancies Complicated by Asthma J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1660 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. McTernan, N. Draper, H. Nicholson, S. M. Chalder, P. Driver, M. Hewison, M. D. Kilby, and P. M. Stewart Reduced Placental 11{beta}-Hydroxysteroid Dehydrogenase Type 2 mRNA Levels in Human Pregnancies Complicated by Intrauterine Growth Restriction: An Analysis of Possible Mechanisms J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4979 - 4983. [Abstract] [Full Text] [PDF]
|
|