Imprinting effects of prenatal overexposure to glucocorticoids on 11?-hydroxysteroid dehydrogenase type 1 expression in rat offspring liver / 第二军医大学学报

ABSTRACT

Objective:To observe the imprinting effects of prenatal overexposure to glucocorticoids on 11?-hydroxysteroid dehydrogenase type 1(11?-HSD1) expression in the rat offspring liver. Methods: Pregnancy was determined by examining vaginal smear. Eight pregnant rats were divided into dexamethasone(DEX) group and normal saline(NS) group at random with each group containing 4 rats.DEX group was given subcutaneous injection of DEX [0.05 mg/(kg?d)] and NS group was given injection of NS.Western blot was adopted to determine 11?-HSD1 protein in the liver of the offspring at the age of 4 months;RT-PCR was used to determine 11?-HSD1 mRNA and hepatic phosphoenolpyruvate carboxykinase(PEPCK) mRNA;and glucose oxidase method was used to measure the blood glucose concentration. Results: Western blot and RT-PCR showed that prenatal overexposure to DEX increased the expression of 11?-HSD1 protein and mRNA in the liver of the female offsprings at 4 months old, but not in male offsprings.Prenatal overexposure to DEX also increased the expression of PEPCK mRNA and blood glucose level in the female offsprings at 4 months old.Conclusion:Our study suggests that prenatal overexposure to glucocorticoids throughout gestation can imprint the expression of 11?-HSD1 in rat offsprings liver, which may lead to the PEPCK overexpression and blood glucose elevation.Development of diabetes may be induced in individuals overexposed to glucocorticoids during fetal period.