Upregulation of Hepatic 11 beta-Hydroxysteroid Dehydrogenase-1 Expression in Calcium-Deficient Rats

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 11 beta-hydroxysteroid dehydrogenase-1 (11 beta-HSD1), 11 beta-HSD2, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor-alpha, 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 11 beta-HSD1 mRNA was upregulated, while hepatic phosphoenolpyruvate carboxykinase expression was downregulated in the low-Ca group. Glucocorticoid receptor, peroxisome proliferator-activated receptor-alpha and 11 beta-HSD2 expression levels showed a similar tendency. Conclusion: A low-Ca diet alters glucocorticoid metabolism, which leads to hepatic up-regulation of 11 beta-HSD1, and is possibly a key mechanism inducing the metabolic complications of Ca deficiency. Copyright (C) 2011 S. Karger AG, Basel