Napolitano A, Voice M W, Edwards C R, Seckl J R, Chapman K E
Molecular Medicine Centre, Western General Hospital, University of Edinburgh, UK.
J Steroid Biochem Mol Biol. 1998 Mar;64(5-6):251-60. doi: 10.1016/s0960-0760(97)00200-8.
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.
11β-羟基类固醇脱氢酶1型（11β-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产物（可的松、11-脱氢皮质酮），从而调节糖皮质激素与受体的结合。11β-HSD-1的表达在发育过程中以及受激素影响，呈现组织特异性调控。该酶在肝脏中高度表达，可能影响糖皮质激素对燃料代谢的作用，而这些过程在脂肪组织中也很重要。在此，我们发现11β-HSD-1在白色脂肪组织中表达，存在于脂肪细胞和基质/血管成分中，也在脂肪细胞系3T3-F442A和3T3-L1中表达。在这些细胞中，11β-HSD-1的表达在分化为脂肪细胞时被诱导，是一个“晚期分化”基因的特征，在达到汇合后6 - 8天表达量最高。在完整的3T3-F442A脂肪细胞中，该酶的作用方向主要是11β-还原，激活惰性糖皮质激素。在用胰岛素、地塞米松或这两种激素联合处理的完全分化的3T3-F442A脂肪细胞中，11β-HSD-1 mRNA的表达变化与甘油-3-磷酸脱氢酶（GPDH）mRNA（编码甘油三酯合成中的关键酶以及脂肪细胞分化的一个特征明确的标志物）相同。脂肪细胞中11β-HSD-1的表达及其在完整3T3-F442A脂肪细胞中的主要还原酶活性表明，11β-HSD-1可能在增强这些细胞中糖皮质激素的作用方面发挥重要作用。3T3-F442A和3T3-L1是有用的模型系统，可用于研究调节11β-HSD-1基因表达的因素以及11β-HSD-1在调节脂肪组织中糖皮质激素作用方面的作用。
