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Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues
Maternal nutrient reduction (MNR) during fetal development may predispose offspring to chronic disease later in life. Increased regeneration of active glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in metabolic tissues is fundamental to the developmental programming of metabol...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609578/ https://www.ncbi.nlm.nih.gov/pubmed/23238295 http://dx.doi.org/10.2337/db12-0561 |
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author | Guo, Chunming Li, Cun Myatt, Leslie Nathanielsz, Peter W. Sun, Kang |
author_facet | Guo, Chunming Li, Cun Myatt, Leslie Nathanielsz, Peter W. Sun, Kang |
author_sort | Guo, Chunming |
collection | PubMed |
description | Maternal nutrient reduction (MNR) during fetal development may predispose offspring to chronic disease later in life. Increased regeneration of active glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in metabolic tissues is fundamental to the developmental programming of metabolic syndrome, but underlying mechanisms are unknown. Hexose-6-phosphate dehydrogenase (H6PD) generates NADPH, the cofactor for 11β-HSD1 reductase activity. CCAAT/enhancer binding proteins (C/EBPs) and the glucocorticoid receptor (GR) regulate 11β-HSD1 expression. We hypothesize that MNR increases expression of fetal C/EBPs, GR, and H6PD, thereby increasing expression of 11β-HSD1 and reductase activity in fetal liver and adipose tissues. Pregnant MNR baboons ate 70% of what controls ate from 0.16 to 0.9 gestation (term, 184 days). Cortisol levels in maternal and fetal circulations increased in MNR pregnancies at 0.9 gestation. MNR increased expression of 11β-HSD1; H6PD; C/EBPα, -β, -γ; and GR in female but not male perirenal adipose tissue and in male but not female liver at 0.9 gestation. Local cortisol level and its targets PEPCK1 and PPARγ increased correspondingly in adipose and liver tissues. C/EBPα and GR were found to be bound to the 11β-HSD1 promoter. In conclusion, sex- and tissue-specific increases of 11β-HSD1, H6PD, GR, and C/EBPs may contribute to sexual dimorphism in the programming of exaggerated cortisol regeneration in liver and adipose tissues and offsprings’ susceptibility to metabolic syndrome. |
format | Online Article Text |
id | pubmed-3609578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-36095782014-04-01 Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues Guo, Chunming Li, Cun Myatt, Leslie Nathanielsz, Peter W. Sun, Kang Diabetes Original Research Maternal nutrient reduction (MNR) during fetal development may predispose offspring to chronic disease later in life. Increased regeneration of active glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in metabolic tissues is fundamental to the developmental programming of metabolic syndrome, but underlying mechanisms are unknown. Hexose-6-phosphate dehydrogenase (H6PD) generates NADPH, the cofactor for 11β-HSD1 reductase activity. CCAAT/enhancer binding proteins (C/EBPs) and the glucocorticoid receptor (GR) regulate 11β-HSD1 expression. We hypothesize that MNR increases expression of fetal C/EBPs, GR, and H6PD, thereby increasing expression of 11β-HSD1 and reductase activity in fetal liver and adipose tissues. Pregnant MNR baboons ate 70% of what controls ate from 0.16 to 0.9 gestation (term, 184 days). Cortisol levels in maternal and fetal circulations increased in MNR pregnancies at 0.9 gestation. MNR increased expression of 11β-HSD1; H6PD; C/EBPα, -β, -γ; and GR in female but not male perirenal adipose tissue and in male but not female liver at 0.9 gestation. Local cortisol level and its targets PEPCK1 and PPARγ increased correspondingly in adipose and liver tissues. C/EBPα and GR were found to be bound to the 11β-HSD1 promoter. In conclusion, sex- and tissue-specific increases of 11β-HSD1, H6PD, GR, and C/EBPs may contribute to sexual dimorphism in the programming of exaggerated cortisol regeneration in liver and adipose tissues and offsprings’ susceptibility to metabolic syndrome. American Diabetes Association 2013-04 2013-03-14 /pmc/articles/PMC3609578/ /pubmed/23238295 http://dx.doi.org/10.2337/db12-0561 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Guo, Chunming Li, Cun Myatt, Leslie Nathanielsz, Peter W. Sun, Kang Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues |
title | Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues |
title_full | Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues |
title_fullStr | Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues |
title_full_unstemmed | Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues |
title_short | Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues |
title_sort | sexually dimorphic effects of maternal nutrient reduction on expression of genes regulating cortisol metabolism in fetal baboon adipose and liver tissues |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609578/ https://www.ncbi.nlm.nih.gov/pubmed/23238295 http://dx.doi.org/10.2337/db12-0561 |
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