| Glucocorticoid hormones (cortisol in humans and most mammals, corticosterone in rodents such as rats and mice) are produced by the adrenal glands. Glucocorticoids play a series of key roles in physiology, maintaining fuel metabolism under basal conditions and underpinning many of the body's adjustments to stressful stimulation. Glucocorticoids exert their effects by binding to the glucocorticoid and mineralocorticoid receptors, both of which are members of the nuclear receptor superfamily. The local availability of glucocorticoids is regulated, in part, by corticosteroid-binding protein (CBG), glucocorticoid receptors (GR) and by the enzyme 11B -hydroxysteroid dehydrogenase (11 P -HSD).There are two types of 11B -HSDs recognized in the body. 11B -HSD1 predominantly acts as a reductase in intact cells converting biologically inert 11-keto GC metabolities into biologically active GC. Thus this enzyme regenerates GC and amplifies GC's actions locally. 11B -HSD2 is an exclusive oxidase converting biologically active GC into its inert products thus attenuating GC's actions locally.During prenatal and early postnatal mammalian development, glucocorticoid levels are generally low, although towards term they rise in many species and effectively signal the onset of late fetal tissue maturation in preparation for extra-uterine existence. Key targets for such late effects include the lung (surfactant secretion), gut, liver, and brain. Indeed, when premature labour threatens, synthetic glucocorticoids, such as dexamethasone, are often exploited to accelerate maturation of the lung and gut. Such therapy efficaciously reduces the incidence of postnatal respiratory distress syndromes.Although GC are indispensable hormones for normal development as well as maturation of the fetus, overexposure to GCs during fetal development causes intrauterine fetal growth retardation (IUGR) and even imprints gene expressions leading to adult diseases, such as diabetes, heart diseases, which are now referred to 'fetal origin of adult disease'. To explain these findings the idea of physiological 'programming' or 'imprinting'in the early life has been proposed. The molecular mechanisms underlying the imprinting effects are not understood, but one hypothesis to explain this 'programming' effect is overexposure of the foetus to glucocorticoids. Many studies have found that prenatal overexposure of the foetus to glucocorticoids could result in low birth weight offspring that develop hypertension, glucose intolerance, insulin resistance, and overactive hypothalamic-pituitary-adrenal (HPA) axis in later life. As we know, 11B-HSD1 could amplify the action of glucocorticoid. It has also been found that the so-called glucocorticoid-associated learning deficit in aged mice was ameliorated in 11B -HSD1 knockout mice. This implies that it is the action of the 11B -HSD1 that results in the changes of the brain's function. As we know, 11 B -HSD1 is most highly expressed in liver, lung, brain and so on. Sequence analysis of the cloned 11B -HSD1 gene revealed a sequence resembling GRE in the promoter region. Our previous study has found that GC could induce the expression of 11B -HSD1 in vitro. However, whether prenatal GC imprints the expression of 11B -HSD1 in the body thus increasing the local actions of GC and thereby programming the occurrence of adult diseases has not been addressed.To address this issue, we studied the effects of prenatal administration of synthetic dexamethasone on the expression of 11 B -HSD1 , GR and in the offsprings' liver after birth. In addition, we studied the effects of prenatal administration of synthetic dexamethasone on the levels of plasma glucose in adult offsprings. Based on our findings, we studied the relationship between the imprinting effects of prenatal overexposure to glucocorticoid on the expression of 11B -HSD1 in offspring's liver and the occurrence of diabetes. Materials and MethodsDrug Adminstration Adult SD rats were maintained under controlled lighting (lights on 7:00-19:00) and temperature (25C), wi...
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