| Corticosterone transfer and metabolism in the dually perfused rat placenta: effect of 11beta-hydroxysteroid dehydrogenase type 2. | |
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MedLine Citation:
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PMID: 16338462 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although rat is the most widely used model of glucocorticoid programming of the fetus, the role of rat placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in the transplacental pharmacokinetics of the naturally occurring glucocorticoid, corticosterone, has not yet been fully elucidated. In this study, expression of 11beta-HSD2 in the rat placenta on two different gestation days (16 and 22) was examined using quantitative RT-PCR and Western blotting, and dually perfused rat term placenta was employed to evaluate its functional capacity to transfer and metabolize corticosterone. Marked decrease in placental expression of 11beta-HSD2 toward term was observed on both mRNA and protein levels. In perfusion studies, increasing maternal corticosterone concentration from 3 to 200 nM resulted in the fall of 11beta-HSD2 conversion capacity from 64.3 to 16.3%, respectively. Enzyme saturation occurred at about 50 nM substrate concentration. When delivering corticosterone (3 or 100 nM) from the fetal side, a similar decline of 11beta-HSD2 conversion capacity was observed (66.5% and 48.5%, respectively). Addition of carbenoxolone (10 or 100 microM), a non-specific 11beta-HSD inhibitor, to maternal perfusate decreased conversion capacity from 66.7 to 12.6 or 8.1%, respectively. Similarly potent inhibitory effect was observed in feto-maternal studies. Neither saturation nor inhibition of 11beta-HSD2 was associated with transformation of corticosterone in metabolites other than 11-dehydrocorticosterone. These data suggest that 11beta-HSD2 is the principal enzyme controlling transplacental passage of corticosterone in rats and is able to eliminate corticosterone in both maternal and fetal circulations. |
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Authors:
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F Staud; K Mazancová; I Miksík; P Pávek; Z Fendrich; J Pácha |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Placenta Volume: 27 ISSN: 0143-4004 ISO Abbreviation: Placenta Publication Date: 2006 Feb-Mar |
Date Detail:
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Created Date: 2005-12-12 Completed Date: 2006-03-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8006349 Medline TA: Placenta Country: England |
Other Details:
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Languages: eng Pagination: 171-80 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, Hradec Králové CZ-500 05, Czech Republic. staud@faf.cuni.cz |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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11-beta-Hydroxysteroid Dehydrogenase Type 2
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antagonists & inhibitors,
genetics,
metabolism* Animals Biological Transport Carbenoxolone / pharmacology Corticosterone / metabolism* Female Perfusion Placenta / enzymology, metabolism, physiology* Pregnancy / metabolism* Rats |
| Chemical | |
Reg. No./Substance:
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50-22-6/Corticosterone; 5697-56-3/Carbenoxolone; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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