Gong Rujun, Morris David J, Brem Andrew S
Rhode Island Hospital, Division of Kidney Diseases and Hypertension, Brown Medical School, Providence, RI 02903, United States.
Steroids. 2008 Oct;73(11):1187-96. doi: 10.1016/j.steroids.2008.05.009. Epub 2008 Jun 3.
Vascular tissue expresses two isoforms of the enzyme 11beta-Hydroxysteroid dehydrogenase, 11beta-HSD1 and 11beta-HSD2. These enzymes are responsible for the local metabolism of endogenous glucocorticoids (GCs). 11beta-HSD1 deactivates GCs to their 11keto metabolites or transforms inert 11keto metabolites back to active GCs. Although, bi-directional, vascular 11beta-HSD1 favors reactivation (reductase) over the deactivation (dehydrogenase) reaction, 11beta-HSD2 only functions as a dehydrogenase. GC deactivation by enhanced 11beta-HSD2 dehydrogenase activity or by impaired 11beta-HSD1 reductase activity correlates with lower vascular resistance. These studies were designed to demonstrate the existence and regulation of these isoforms in vascular endothelial cells and to determine whether the expression varied by species and locale. Western blots were prepared from pre-confluent and confluent cultures of human umbilical vein endothelial cells (HUVEC). 11beta-HSD1 was clearly expressed while 11beta-HSD2 was much less prominent. Cultured rat aortic and bovine glomerular endothelial cells showed a similar pattern. Using immunohistochemistry, endothelial cells from human and mouse artery preparations clearly demonstrated 11beta-HSD1. In separate experiments, pre-confluent growing HUVEC expressed more 11beta-HSD1 compared to confluent cells. Serum-deprived growth-retarded HUVEC expressed significantly less 11beta-HSD1. The enhanced expression of 11beta-HSD1 was also observed 24h following a scratch "injury" to the culture plates. Changes in 11beta-HSD1 with growth and during repair occurred at the transcription level. Thus, 11beta-HSD1 protein expression predominates in endothelial cells and varies during periods of growth.
血管组织表达11β-羟基类固醇脱氢酶的两种同工型，即11β-HSD1和11β-HSD2。这些酶负责内源性糖皮质激素（GCs）的局部代谢。11β-HSD1将GCs失活为其11-酮代谢产物，或将无活性的11-酮代谢产物转化回活性GCs。虽然血管11β-HSD1的作用是双向的，但相比失活（脱氢酶）反应，它更倾向于再激活（还原酶）反应，而11β-HSD2仅作为脱氢酶发挥作用。通过增强11β-HSD2脱氢酶活性或削弱11β-HSD1还原酶活性使GC失活，与较低的血管阻力相关。这些研究旨在证明这些同工型在血管内皮细胞中的存在和调节，并确定其表达是否因物种和部位而异。从人脐静脉内皮细胞（HUVEC）的汇合前和汇合培养物中制备了蛋白质免疫印迹。11β-HSD1明显表达，而11β-HSD2则不太明显。培养的大鼠主动脉和牛肾小球内皮细胞呈现出类似的模式。使用免疫组织化学方法，人及小鼠动脉制剂中的内皮细胞清楚地显示出11β-HSD1。在单独的实验中，与汇合细胞相比，汇合前生长的HUVEC表达更多的11β-HSD1。血清剥夺导致生长迟缓的HUVEC表达的11β-HSD1明显减少。在培养板划痕“损伤”后24小时也观察到11β-HSD1的表达增强。11β-HSD1随生长和修复过程的变化发生在转录水平。因此，11β-HSD1蛋白表达在内皮细胞中占主导地位，并在生长期间发生变化。
