HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited 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 My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sampath-Kumar, R. Articles by Yang, K. Search for Related Content PubMed PubMed Citation Articles by Sampath-Kumar, R. Articles by Yang, K. Agricola Articles by Sampath-Kumar, R. Articles by Yang, K.

11ß-Hydroxysteroid Dehydrogenase Type 2 Is the Predominant Isozyme in the Guinea Pig Placenta: Decreases in Messenger Ribonucleic Acid and Activity at Term¹

^a The Lawson Research Institute, St. Joseph's Hospital, Departments of Obstetrics&Gynecology and Physiology, University of Western Ontario, London, Ontario, Canada N6A 4V2 ^b Departments of Physiology and Obstetrics&Gynecology, University of Toronto, Toronto, Ontario, Canada M5S 1A8

The type 2 isozyme of 11ß-hydroxysteroid dehydrogenase (11ß-HSD2) is responsible for inactivating physiologically active glucocorticoids to their inert metabolites. This is the predominant 11ß-HSD isozyme in the human placenta, where it is believed to protect the fetus from high levels of maternal cortisol. Given the similarity in placental structure between the human and the guinea pig (hemomonochorial), we have evaluated the potential of utilizing the guinea pig as a model to study the function and regulation of placental 11ß-HSD2 in fetal development. In this study, we characterized the intrinsic properties of 11ß-HSD in the guinea pig placenta during late pregnancy. The 11ß-HSD activity in the placenta was characteristic of 11ß-HSD2 in that it possessed only dehydrogenase activity that was NAD-dependent and had a high affinity for cortisol (K_m = 134 nM). Moreover, the level of the 11ß-HSD2-like activity decreased significantly at term. To verify the expression of 11ß-HSD2 gene and to determine whether corresponding changes in 11ß-HSD2 mRNA occur at term, we also cloned the cDNA encoding guinea pig placental 11ß-HSD2. The deduced guinea pig 11ß-HSD2 enzyme contains 395 amino acids and shares over 80% sequence identity with other mammalian 11ß-HSD2 proteins. Northern blot analyses demonstrated the presence of the mRNA for 11ß-HSD2 but not that for 11ß-HSD1. Moreover, the level of 11ß-HSD2 mRNA decreased significantly at term. The parallel decrease in levels of 11ß-HSD2 activity and mRNA at term is consistent with, and provides a plausible molecular basis for, the previously reported increase in the rate of placental transfer of cortisol between mother and fetus at that time. In conclusion, the present study demonstrates that the guinea pig resembles the human in that 11ß-HSD2 is the predominant, if not exclusive, isozyme expressed in the placenta. Therefore, the guinea pig appears to represent a suitable model in which to study the role of placental 11ß-HSD2 in human fetal development.

¹ This work was supported by the Canadian MRC (Grant MT-12100 to K.Y.) and NSERC (Operating Grant to S.G.M.). K.Y. is an Ontario Ministry of Health Career Scientist.

² Correspondence: K. Yang, Lawson Research Institute, 268 Grosvenor Street, London, ON, Canada N6A 4V2. FAX: 519 646 6110; kyang{at}julian.uwo.ca

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]

				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]

				A. Kapoor, E. Dunn, A. Kostaki, M. H. Andrews, and S. G. Matthews Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids J. Physiol., April 1, 2006; 572(1): 31 - 44. [Abstract] [Full Text] [PDF]

				G. M. Kalabis, A. Kostaki, M. H. Andrews, S. Petropoulos, W. Gibb, and S. G. Matthews Multidrug Resistance Phosphoglycoprotein (ABCB1) in the Mouse Placenta: Fetal Protection Biol Reprod, October 1, 2005; 73(4): 591 - 597. [Abstract] [Full Text] [PDF]

				A. Kapoor and S. G Matthews Short periods of prenatal stress affect growth, behaviour and hypothalamo-pituitary-adrenal axis activity in male guinea pig offspring J. Physiol., August 1, 2005; 566(3): 967 - 977. [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]