Sexually dimorphic effects of maternal nutrient reduction on expression of genes regulating cortisol metabolism in fetal baboon adipose and liver tissues

Chunming Guo, Cun Li, Leslie Myatt, Peter W. Nathanielsz, Kang Sun

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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,-g; 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.

Original languageEnglish (US)
Pages (from-to)1175-1185
Number of pages11
JournalDiabetes
Volume62
Issue number4
DOIs
StatePublished - Apr 2013
Externally publishedYes

Fingerprint

11-beta-Hydroxysteroid Dehydrogenases
Papio
CCAAT-Enhancer-Binding Proteins
Hydrocortisone
Adipose Tissue
Glucocorticoid Receptors
Mothers
Gene Expression
Food
Liver
Pregnancy
Oxidoreductases
Fetal Proteins
Peroxisome Proliferator-Activated Receptors
Liver Regeneration
Fetal Development
NADP
Sex Characteristics
Glucocorticoids
Regeneration

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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.

In: Diabetes, Vol. 62, No. 4, 04.2013, p. 1175-1185.

Research output: Contribution to journalArticle

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