| Glucocorticoids (GC) are synthesized and secreted by the adrenal cortex. GC not only play a vital role in maintaining metabolic and stress processes, but also take part in the development and maturation of nervous system. The actions of GC on nervous system are regulated at both receptor and pre-receptor levels. There are two types of corticosteroid receptors, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). At the receptor level, GC binds to both MR and GR, but with higher affinity for MR than GR. At the pre-receptor level, the amounts of GC binding to the receptors are determined by glucocorticoid binding proteins as well as 11(-hydroxysteroid dehydrogenases (11(-HSDs). There are two types of 11(-HSDs recognized in the body. 11(-HSD1 predominantly acts as a reductase in tact cells converting biologically inert 11-keto GC metabolites into biologically active GC. Thus this enzyme regenerates GC and amplifies GC's actions locally. 11(-HSD2 is an exclusive oxidase converting biologically active GC into its inert products thus attenuating GC's actions. During early and mid-gestations, GC levels are kept low in the fetal circulation to ensure normal development of the fetus. The expression of 11(-HSD1 in the fetal brain starts in the late gestation and gradually increases with gestational age, while the expression of 11(-HSD2 starts around mid-gestation and decreases dramatically towards term. The decrease of 11(-HSD2 expression and the increase of 11(-HSD1 expression in the late gestation may allow GC's activation of more GR in the brain, thus permitting neuronal and glial maturational events. However, the rat gives birth to immature young, much development and maturation of the nervous system occurs in the postnatal period, which resembles the human fetal brain development in late gestation. Therefore the understanding of 11?-HSD development in the neonatal rat is more helpful for us to understand the role of11?-HSD 1 in human fetal brain development.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 imprinting gene expressions leading to adult diseases. Recently it has been reported that altered sensitivity to GC themselves is a potential molecular target underlying GC's imprinting effects. It has been demonstrated that prenatal GC treatment permanently reduced the expression of GR in the CNS. Sequence analysis of the cloned 11(-HSD1 gene revealed a sequence resembling GRE in the promoter region. There are evidences showing that GC regulates the expression of 11(-HSD1 both in vitro and vivo. However, whether prenatal GC imprints the pre-receptor 11(-HSD1 expression and increases the actions of GC on the brain in the adult has not been addressed. To address the above issues, we examined the distribution and expression of 11(-HSD1 in the neonatal rat brain, and the co-localization of 11(-HSD1 and GR in the hippocampus of the neonatal rat. In addition, we studied the effects of prenatal administration of synthetic dexamethasone on the expression of 11β-HSD1 in the rat hippocampus after birth. Further more, the underlying glucocorticoid receptor subtypes as well as the involvement of 11(-HSD1 gene promoter in the up-regulation of 11β-HSD1 expression by GC were also investigated.METHODS1. Immunohistochemistry was employed to investigate the distribution of 11β-HSD1 as well as the co-localization of 11β-HSD1 and GR in the neonatal brain.2. Western blot was used to study the developmental expressions of 11β-HSD1 protein in the different brain areas.3. The developmental expressions of 11β-HSD1 in the hippocampus of the rat prenatally exposed to dexamethasone (DEX) were determined by Western blot as well as thin layer chromatography (TLC) method.4. The receptor subtypes underlying up-regulation of 11β-HSD1 protein by glucocorticoid were explored by using Western blot and TLC.5. The involv...
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