11Beta-hydroxysteroid dehydrogenase 1 in adipocytes: expression is differentiation-dependent and hormonally regulated.
11Beta-hydroxysteroid dehydrogenase 1 in adipocytes: expression is differentiation-dependent and hormonally regulated.
复制标题
脂肪细胞中的 11β-羟基类固醇脱氢酶 1：表达依赖于分化并受激素调节。
DOI：
--
复制
发表时间：
1998
影响因子：
4.1
通讯作者：
K. E. Chapman
中科院分区：
文献类型：
--
作者：
A. Napolitano;M. Voice;C. R. Edwards;J. Seckl;K. E. Chapman
11 β-羟基类固醇脱氢酶1型（11 β-HSD-1）催化生理性糖皮质激素（皮质醇、皮质酮）可逆代谢为无活性代谢物（可的松、11-脱氢皮质酮），从而调节糖皮质激素进入受体。11 β-HSD-1的表达在发育过程中受到激素的调节，并以组织特异性的方式进行调节。该酶在肝脏中高度表达，在肝脏中它可能影响糖皮质激素对燃料代谢的作用，该过程在脂肪组织中也很重要。在这里，我们表明，11 β-HSD-1表达在白色脂肪组织，在脂肪细胞和基质/血管区室，并在脂肪细胞系3 T3-F442 A和3 T3-L1。在这些细胞中，11 β-HSD-1表达在分化成脂肪细胞时被诱导，并且是“晚期分化”基因的特征，在达到汇合后6-8天表达最大。在完整的3 T3-F442 A脂肪细胞中，酶的方向主要是11 β-还原，激活惰性糖皮质激素。在用胰岛素、地塞米松或激素组合处理的完全分化的3 T3-F442 A脂肪细胞中，11 β-HSD-1 mRNA的表达以与甘油-3-磷酸脱氢酶（GPDH）mRNA（编码甘油三酯合成中的关键酶和脂肪细胞分化的充分表征的标志物）相同的方式改变。11 β-HSD-1在脂肪细胞中的表达及其在完整的3 T3-F442 A脂肪细胞中的主要还原酶活性的证明表明，11 β-HSD-1可能在增强这些细胞中的糖皮质激素作用中起重要作用。3 T3-F442 A和3 T3-L1代表了有用的模型系统，在其中检测调节11 β-HSD-1基因表达的因子和11 β-HSD-1在调节脂肪组织中糖皮质激素作用中的作用。
11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyses the reversible metabolism of physiological glucocorticoids (cortisol, corticosterone) to inactive metabolites (cortisone, 11-dehydrocorticosterone), thus regulating glucocorticoid access to receptors. 11Beta-HSD-1 expression is regulated during development and by hormones in a tissue specific manner. The enzyme is highly expressed in liver, where it may influence glucocorticoid action on fuel metabolism, processes also important in adipose tissue. Here we show that 11beta-HSD-1 is expressed in white adipose tissue, in both the adipocyte and stromal/vascular compartments, and in the adipocyte cell lines 3T3-F442A and 3T3-L1. In these cells, 11beta-HSD-1 expression is induced upon differentiation into adipocytes and is characteristic of a 'late differentiation' gene, with maximal expression 6-8 days after confluence is reached. In intact 3T3-F442A adipocytes the enzyme direction is predominantly 11beta-reduction, activating inert glucocorticoids. The expression of 11beta-HSD-1 mRNA is altered in fully differentiated 3T3-F442A adipocytes treated with insulin, dexamethasone or a combination of the hormones, in an identical manner to glycerol-3-phosphate dehydrogenase (GPDH) mRNA (encoding a key enzyme in triglyceride synthesis and a well-characterised marker of adipocyte differentiation). The demonstration of 11beta-HSD-1 expression in adipocytes and its predominant reductase activity in intact 3T3-F442A adipocytes suggests that 11beta-HSD-1 may play an important role in potentiating glucocorticoid action in these cells. 3T3-F442A and 3T3-L1 represent useful model systems in which to examine the factors which regulate 11beta-HSD-1 gene expression and the role of 11beta-HSD-1 in modulating glucocorticoid action in adipose tissue.