title: Prenatal programming of metabolic syndrome in the common marmoset is associated with increased expression of 11beta-hydroxysteroid dehydrogenase type 1.
abstract: OBJECTIVE
  Recent studies in humans and animal models of obesity have shown increased adipose tissue activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which amplifies local tissue glucocorticoid concentrations. The reasons for this 11beta-HSD1 dysregulation are unknown. Here, we tested whether 11beta-HSD1 expression, like the metabolic syndrome, is "programmed" by prenatal environmental events in a nonhuman primate model, the common marmoset monkey.
  
  
  METHODS
  We used a "fetal programming" paradigm where brief antenatal exposure to glucocorticoids leads to the metabolic syndrome in the offspring. Pregnant marmosets were given the synthetic glucocorticoid dexamethasone orally for 1 week in either early or late gestation, or they were given vehicle. Tissue 11beta-HSD1 and glucocorticoid receptor mRNA expression were examined in the offspring at 4 and 24 months of age.
  
  
  RESULTS
  Prenatal dexamethasone administration, selectively during late gestation, resulted in early and persistent elevations in 11beta-HSD1 mRNA expression and activity in the liver, pancreas, and subcutaneous-but not visceral-fat. The increase in 11beta-HSD1 occurred before animals developed obesity or overt features of the metabolic syndrome. In contrast to rodents, in utero dexamethasone exposure did not alter glucocorticoid receptor expression in metabolic tissues in marmosets.
  
  
  CONCLUSIONS
  These data suggest that long-term upregulation of 11beta-HSD1 in metabolically active tissues may follow prenatal "stress" hormone exposure and indicates a novel mechanism for fetal origins of adult obesity and the metabolic syndrome.
authors.affiliation: Endocrinology Unit, Queen's Medical Research Institute, University of Edinburgh, U.K.
authors.forename: Moffat J
authors.initials: MJ
authors.lastname: Nyirenda
authors.forename: Roderick
authors.initials: R
authors.lastname: Carter
authors.forename: Justin I
authors.initials: JI
authors.lastname: Tang
authors.forename: Annick
authors.initials: A
authors.lastname: de Vries
authors.forename: Christina
authors.initials: C
authors.lastname: Schlumbohm
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Hillier
authors.forename: Frank
authors.initials: F
authors.lastname: Streit
authors.forename: Michael
authors.initials: M
authors.lastname: Oellerich
authors.forename: Victor W
authors.initials: VW
authors.lastname: Armstrong
authors.forename: Eberhard
authors.initials: E
authors.lastname: Fuchs
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology*; D000375:Aging / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002144:Callithrix; D003907:Dexamethasone; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D014280:Triglycerides; D003907:Dexamethasone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1