title: Sexually dimorphic effects of maternal nutrient reduction on expression of genes regulating cortisol metabolism in fetal baboon adipose and liver tissues.
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, -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.
authors.affiliation: Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Chunming
authors.initials: C
authors.lastname: Guo
authors.forename: Cun
authors.initials: C
authors.lastname: Li
authors.forename: Leslie
authors.initials: L
authors.lastname: Myatt
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nathanielsz
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
mesh_terms: D000273:Adipose Tissue / Q000196:embryology / Q000378:metabolism*; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000502:physiology; D005508:Food Deprivation; D005786:Gene Expression Regulation / Q000502:physiology*; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D010215:Papio; D011247:Pregnancy; D011897:Random Allocation; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D006854:Hydrocortisone