title: Upregulation of hepatic 11β-hydroxysteroid dehydrogenase-1 expression in calcium-deficient rats.
abstract: BACKGROUND
  Many epidemiologic studies have reported a link between calcium (Ca) deficiency and metabolic syndrome. In this study, we examine Ca deficiency in rats and whether changes in glucocorticoid metabolism are induced.
  
  
  METHODS
  Twelve-week-old female Wistar rats were weaned onto a very-low-Ca diet (low-Ca group) or a control diet (control group) for 2 weeks. Quantitative real-time PCR was used to assess mRNA for 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1), 11β-HSD2, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor-α, and glucocorticoid receptor in the liver. Concentrations of adiponectin, leptin, corticosterone, intact parathyroid hormone, asymmetrical dimethylarginine and insulin in fasting serum were determined using a rat-specific enzyme-linked immunosorbent assay. Glucose concentrations were measured using a glucose oxidase system. Serum ionized Ca levels were measured with an automatic ion-selective electrode analyzer. Serum nitrite/nitrate levels were measured using a colorimetric assay kit.
  
  
  RESULTS
  After 2 weeks, no differences in serum glucose, corticosterone or insulin levels were observed. The low-Ca group rats showed higher homeostasis model assessment insulin resistance, lower adiponectin and higher intact parathyroid hormone levels. Serum nitrite/nitrate and asymmetrical dimethylarginine were significantly higher in the low-Ca group than in the control group. The expression of hepatic 11β-HSD1 mRNA was upregulated, while hepatic phosphoenolpyruvate carboxykinase expression was downregulated in the low-Ca group. Glucocorticoid receptor, peroxisome proliferator-activated receptor-α and 11β-HSD2 expression levels showed a similar tendency.
  
  
  CONCLUSIONS
  A low-Ca diet alters glucocorticoid metabolism, which leads to hepatic upregulation of 11β-HSD1, and is possibly a key mechanism inducing the metabolic complications of Ca deficiency.
authors.affiliation: Department of Pediatrics, Kansai Medical University, Moriguchi, Japan. takaya@takii.kmu.ac.jp
authors.forename: Junji
authors.initials: J
authors.lastname: Takaya
authors.forename: Anna
authors.initials: A
authors.lastname: Iharada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okihana
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kaneko
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002118:Calcium / Q000097:blood / Q000172:deficiency*; D003345:Corticosterone / Q000097:blood; D004032:Diet; D005260:Female; D007328:Insulin / Q000097:blood; D017736:Ion-Selective Electrodes; D020738:Leptin / Q000097:blood; D008099:Liver / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D002118:Calcium; D003345:Corticosterone