11β-hydroxysteroid dehydrogenase type 1 （11β-HSD1） and type 2 （11β-HSD2） are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and lo...11β-hydroxysteroid dehydrogenase type 1 （11β-HSD1） and type 2 （11β-HSD2） are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and localization of 11β-HSD in rat testis during postnatal development, and the regulation of these genes by luteinizing hormone （LH） and androgens, mRNA and protein levels were analyzed by quantitative real-time-polymerase chain reaction and western blotting, respectively, in testes collected from rats at postnatal day （PND） 7, 14, 21, 35, and 90, and from rats treated with LH, 7α.methyl-19-nortestosterone （MENT） and testosterone at PND 21 and PND 90. Immunohistochemical staining was used to identify the localization of the 11β-HSD in rat testis at PND 7, 14, and 90. We found that 11β-HSD1 expression was restricted to the interstitial areas, and that its levels increased during rat testis development. In contrast, whereas 11β-HSD2 was expressed in both the interstitial areas and seminiferous tubules at PND 7, it was present only in the interstitial areas at PND 90, and its levels declined during testicular development. Moreover, 11β-HSD1 mRNA was induced by LH in both the PND 21 and 90 testes and by MENT at PND 21, whereas 11β-HSD2 mRNA was induced by testosterone and MENT in the PND 21 testis and by LH in the PND 90 testis. In conclusion, our study indicates that the 11β-HSD1 and 11β-HSD2 genes have distinct patterns of spatiotemporal expression and hormonal regulation during postnatal development of the rat testis.展开更多
It has been proposed that 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which activates glucocorticoids, plays a role in chronic inflammatory diseases including metabolic diseases, rheumatoid arthritis, and ul...It has been proposed that 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which activates glucocorticoids, plays a role in chronic inflammatory diseases including metabolic diseases, rheumatoid arthritis, and ulcerative colitis. We have recently reported that the expression of 11β-HSD1 is increased in the gingiva of patients with chronic periodontitis and in that of rats with ligature-induced periodontitis. In this study, to further demonstrate the involvement of 11β-HSD1 in chronic periodontitis, the expression of 11β-HSD1 was investigated in another rat model of experimental periodontitis induced by intragingival injection of lipopolysaccharide from Porphyromonas gingivalis (LPS-PG). Alveolar bone loss was observed two weeks after intragingival injection of LPS-PG. The level of 11β-HSD1 mRNA assessed by real-time reverse transcriptase-polymerase chain reaction was significantly elevated in LPS-PG-induced periodontitis compared with controls. The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates glucocorticoids, was not significantly different between control and LPS-PG-induced periodontitis. The expression of 11β-HSD1 was significantly correlated with that of TNF in LPS-PG-induced periodontitis. The increased expression of 11β-HSD1 protein in LPS-PG-induced periodontitis was confirmed by immunohistochemistry using anti-11β-HSD1 antibody. These results further suggest a role for 11β-HSD1 in the pathogenesis of chronic periodontitis.展开更多
目的研究原发性高血压(essential hypertension,EH)患者11β-类固醇脱氢酶2(11 beta-hydroxysteroid dehydrogenase type 2,11β-HSD2)基因甲基化表达,探讨原发性高血压的发病机制。方法选取2018年1月至2019年6月在佳木斯医学院第一附...目的研究原发性高血压(essential hypertension,EH)患者11β-类固醇脱氢酶2(11 beta-hydroxysteroid dehydrogenase type 2,11β-HSD2)基因甲基化表达,探讨原发性高血压的发病机制。方法选取2018年1月至2019年6月在佳木斯医学院第一附属医院未经治疗的EH患者71例为EH组,选取我院体检的50例健康志愿者为正常对照组,应用甲基化特异性PCR(methylation specific PCR,MSP)方法检测所有入选研究对象11β-HSD2基因甲基化表达。结果EH组和对照组11β-HSD2基因甲基化表达比较,差异具有统计学意义(P<0.05)。结论11β-HSD2基因甲基化参与EH的发生。展开更多
The metabolic syndrome, one of the most common clinical conditions in recent times, represents a combination of cardiometabolic risk determinants, including central obesity, glucose intolerance, insulin resistance, dy...The metabolic syndrome, one of the most common clinical conditions in recent times, represents a combination of cardiometabolic risk determinants, including central obesity, glucose intolerance, insulin resistance, dyslipidemia, non-alcoholic fatty liver disease and hypertension. Prevalence of the metabolic syndrome is rapidly increasing worldwide as a consequence of common overnutrition and consequent obesity. Although a unifying picture of the pathomechanism is still missing, the key role of the pre-receptor glucocorticoid activation has emerged recently. Local glucocorticoid activation is catalyzed by a triad composed of glucose-6-phosphate-transporter, hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase type 1 in the endoplasmic reticulum. The elements of this system can be found in various cell types, including adipocytes and hepatocytes. While the contribution of glucocorticoid activation in adipose tissue to the pathomechanism of the metabolic syndrome has been well established, the relative importance of the hepatic process is less understood. This review summarizes the available data on the role of the hepatic triad and its role in the metabolic syndrome, by confronting experimental findings with clinical observations.展开更多
过量激素刺激骨髓间质干细胞(bone marrow stromal cells,BMSCs)使得成骨能力减弱、成脂能力增强是导致股骨头坏死(osteonecrosis of the femoral head,ONFH)的主要原因,调控机制尚未阐明。最新的研究发现激素引起骨组织中11β-HSD1活...过量激素刺激骨髓间质干细胞(bone marrow stromal cells,BMSCs)使得成骨能力减弱、成脂能力增强是导致股骨头坏死(osteonecrosis of the femoral head,ONFH)的主要原因,调控机制尚未阐明。最新的研究发现激素引起骨组织中11β-HSD1活性增强,导致骨局部内源性激素积聚可抑制骨形成。抑制11β-HSD1活性可促进成骨细胞分化,抑制脂肪分化。故推测内源性激素在ONFH的发病过程中起到重要作用,在激素与BMSCs活性变化之间可能存在11β-HSD1调控的内源性激素代谢途径参与ONFH的发病过程。因此,深入研究11β-HSD1介导的内源性激素代谢途径在ONFH发病中的作用,对深入了解ONFH的发病机制具有重要意义。展开更多
目的探讨心房颤动患者心房肌组织盐皮质激素受体(MR)和赋予 MR 特异性的关键酶11β-羟基类固醇脱氢酶Ⅱ(11βHSD2)的 mRNA 和蛋白表达改变。方法入选进行人工心脏瓣膜置换术的风湿性心脏病患者25例,其中窦性心律12例,慢性心房颤动(心房...目的探讨心房颤动患者心房肌组织盐皮质激素受体(MR)和赋予 MR 特异性的关键酶11β-羟基类固醇脱氢酶Ⅱ(11βHSD2)的 mRNA 和蛋白表达改变。方法入选进行人工心脏瓣膜置换术的风湿性心脏病患者25例,其中窦性心律12例,慢性心房颤动(心房颤动时程≥6月)13例。术前进行经胸超声心动图检查,所有患者在术前均签订知情同意书,于手术时取左右心房侧壁组织。用实时荧光定量 PCR 检测 MR 和11βHSD2的 mRNA 水平,Western 印迹检测 MR 和11βHSD2的蛋白表达改变。结果心房颤动组比窦性心律组左房内径显著扩大(P<0.01);房颤组患者 MR mRNA表达(右房:5.37±1.15 vs 2.67±1.09,左房:5.19±1.14 vs 2.70±0.82 P 均<0.01)和11βHSD2mRNA 表达(右房:0.86±0.14 vs 0.33±0.12,左房:0.95±0.15 vs 0.37±0.10 P 均<0.01)均明显增加;同时房颤组患者 MR 和11βHSD2蛋白表达也较窦性心律者明显增加,MR 分别为右房:1.65±0.72 vs 0.86±0.33(P<0.01);左房:1.72±0.62 vs 0.97±0.37(P<0.05)。11βHSD2分别为右房:-1.18±0.64 vs 0.71+0.21(P<0.01);左房:1.36±0.58 vs 0.85±0.15(P<0.05);但在左右心房之间无论是在窦性心律或心房颤动时,MR 和11βHSD2二者在 mRNA 水平和蛋白表达水平差异均无统计学意义(P>0.05)。结论心房颤动时心房肌组织 MR 和11βHSD2表达增加,醛固酮受体拮抗剂将可能对心房颤动发挥治疗作用。展开更多
目的研究小檗碱对胰岛素抵抗模型肝细胞11β-羟基类固醇脱氢酶1（11β-HSD1）mRNA表达的影响。方法应用高浓度胰岛素孵育HepG2细胞24h，建立胰岛素抵抗肝细胞模型。将模型细胞分别置于含不同浓度胰岛素和小檗碱的培养液中培养24h，以葡...目的研究小檗碱对胰岛素抵抗模型肝细胞11β-羟基类固醇脱氢酶1（11β-HSD1）mRNA表达的影响。方法应用高浓度胰岛素孵育HepG2细胞24h，建立胰岛素抵抗肝细胞模型。将模型细胞分别置于含不同浓度胰岛素和小檗碱的培养液中培养24h，以葡萄糖氧化酶-过氧化物酶（GOD-POD）法测定培养液中的葡萄糖浓度，计算细胞对葡萄糖的吸收率。应用RT-PCR检测小檗碱作用前后模型细胞11β-HSD1mRNA的表达。结果以含10-7mol／L胰岛素的培养液孵育HepG2细胞24h后，细胞对葡萄糖的吸收明显降低，表明建模成功。模型细胞经高浓度（10μmol／L）小檗碱处理后，葡萄糖吸收率明显增加[（42．53±1．99）％VS（28．16±1．99）％，t=12．9457，P〈0．01]，并且高浓度小檗碱与胰岛素对模型细胞有协同促进葡萄糖吸收的作用。模型细胞11β—HSD 1mRNA表达显著高于非胰岛素抵抗细胞（相对表达量：4．60±0．96 vs 0．67±0．42，t=4．9476，P〈0．05）。经高浓度小檗碱干预24h后，模型细胞11β-HSD1mRNA表达降低，与非胰岛素抵抗HepG2细胞相比差异无统计学意义（相对表达量：1．12±0．35VS0．67±0．42，t=1．1394，P〉0．05）。低浓度（1μmol／L）小檗碱则作用不明显。结论浓度依赖性地下调11β—HSD1mRNA表达是小檗碱改善胰岛素抵抗的作用机制之一。展开更多
文摘11β-hydroxysteroid dehydrogenase type 1 （11β-HSD1） and type 2 （11β-HSD2） are expressed in rat testis, where they regulate the local concentrations of glucocorticoids. Here, we investigated the expression and localization of 11β-HSD in rat testis during postnatal development, and the regulation of these genes by luteinizing hormone （LH） and androgens, mRNA and protein levels were analyzed by quantitative real-time-polymerase chain reaction and western blotting, respectively, in testes collected from rats at postnatal day （PND） 7, 14, 21, 35, and 90, and from rats treated with LH, 7α.methyl-19-nortestosterone （MENT） and testosterone at PND 21 and PND 90. Immunohistochemical staining was used to identify the localization of the 11β-HSD in rat testis at PND 7, 14, and 90. We found that 11β-HSD1 expression was restricted to the interstitial areas, and that its levels increased during rat testis development. In contrast, whereas 11β-HSD2 was expressed in both the interstitial areas and seminiferous tubules at PND 7, it was present only in the interstitial areas at PND 90, and its levels declined during testicular development. Moreover, 11β-HSD1 mRNA was induced by LH in both the PND 21 and 90 testes and by MENT at PND 21, whereas 11β-HSD2 mRNA was induced by testosterone and MENT in the PND 21 testis and by LH in the PND 90 testis. In conclusion, our study indicates that the 11β-HSD1 and 11β-HSD2 genes have distinct patterns of spatiotemporal expression and hormonal regulation during postnatal development of the rat testis.
文摘It has been proposed that 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which activates glucocorticoids, plays a role in chronic inflammatory diseases including metabolic diseases, rheumatoid arthritis, and ulcerative colitis. We have recently reported that the expression of 11β-HSD1 is increased in the gingiva of patients with chronic periodontitis and in that of rats with ligature-induced periodontitis. In this study, to further demonstrate the involvement of 11β-HSD1 in chronic periodontitis, the expression of 11β-HSD1 was investigated in another rat model of experimental periodontitis induced by intragingival injection of lipopolysaccharide from Porphyromonas gingivalis (LPS-PG). Alveolar bone loss was observed two weeks after intragingival injection of LPS-PG. The level of 11β-HSD1 mRNA assessed by real-time reverse transcriptase-polymerase chain reaction was significantly elevated in LPS-PG-induced periodontitis compared with controls. The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates glucocorticoids, was not significantly different between control and LPS-PG-induced periodontitis. The expression of 11β-HSD1 was significantly correlated with that of TNF in LPS-PG-induced periodontitis. The increased expression of 11β-HSD1 protein in LPS-PG-induced periodontitis was confirmed by immunohistochemistry using anti-11β-HSD1 antibody. These results further suggest a role for 11β-HSD1 in the pathogenesis of chronic periodontitis.
文摘目的研究原发性高血压(essential hypertension,EH)患者11β-类固醇脱氢酶2(11 beta-hydroxysteroid dehydrogenase type 2,11β-HSD2)基因甲基化表达,探讨原发性高血压的发病机制。方法选取2018年1月至2019年6月在佳木斯医学院第一附属医院未经治疗的EH患者71例为EH组,选取我院体检的50例健康志愿者为正常对照组,应用甲基化特异性PCR(methylation specific PCR,MSP)方法检测所有入选研究对象11β-HSD2基因甲基化表达。结果EH组和对照组11β-HSD2基因甲基化表达比较,差异具有统计学意义(P<0.05)。结论11β-HSD2基因甲基化参与EH的发生。
基金Supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences to Csala M
文摘The metabolic syndrome, one of the most common clinical conditions in recent times, represents a combination of cardiometabolic risk determinants, including central obesity, glucose intolerance, insulin resistance, dyslipidemia, non-alcoholic fatty liver disease and hypertension. Prevalence of the metabolic syndrome is rapidly increasing worldwide as a consequence of common overnutrition and consequent obesity. Although a unifying picture of the pathomechanism is still missing, the key role of the pre-receptor glucocorticoid activation has emerged recently. Local glucocorticoid activation is catalyzed by a triad composed of glucose-6-phosphate-transporter, hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase type 1 in the endoplasmic reticulum. The elements of this system can be found in various cell types, including adipocytes and hepatocytes. While the contribution of glucocorticoid activation in adipose tissue to the pathomechanism of the metabolic syndrome has been well established, the relative importance of the hepatic process is less understood. This review summarizes the available data on the role of the hepatic triad and its role in the metabolic syndrome, by confronting experimental findings with clinical observations.
文摘过量激素刺激骨髓间质干细胞(bone marrow stromal cells,BMSCs)使得成骨能力减弱、成脂能力增强是导致股骨头坏死(osteonecrosis of the femoral head,ONFH)的主要原因,调控机制尚未阐明。最新的研究发现激素引起骨组织中11β-HSD1活性增强,导致骨局部内源性激素积聚可抑制骨形成。抑制11β-HSD1活性可促进成骨细胞分化,抑制脂肪分化。故推测内源性激素在ONFH的发病过程中起到重要作用,在激素与BMSCs活性变化之间可能存在11β-HSD1调控的内源性激素代谢途径参与ONFH的发病过程。因此,深入研究11β-HSD1介导的内源性激素代谢途径在ONFH发病中的作用,对深入了解ONFH的发病机制具有重要意义。
文摘目的探讨心房颤动患者心房肌组织盐皮质激素受体(MR)和赋予 MR 特异性的关键酶11β-羟基类固醇脱氢酶Ⅱ(11βHSD2)的 mRNA 和蛋白表达改变。方法入选进行人工心脏瓣膜置换术的风湿性心脏病患者25例,其中窦性心律12例,慢性心房颤动(心房颤动时程≥6月)13例。术前进行经胸超声心动图检查,所有患者在术前均签订知情同意书,于手术时取左右心房侧壁组织。用实时荧光定量 PCR 检测 MR 和11βHSD2的 mRNA 水平,Western 印迹检测 MR 和11βHSD2的蛋白表达改变。结果心房颤动组比窦性心律组左房内径显著扩大(P<0.01);房颤组患者 MR mRNA表达(右房:5.37±1.15 vs 2.67±1.09,左房:5.19±1.14 vs 2.70±0.82 P 均<0.01)和11βHSD2mRNA 表达(右房:0.86±0.14 vs 0.33±0.12,左房:0.95±0.15 vs 0.37±0.10 P 均<0.01)均明显增加;同时房颤组患者 MR 和11βHSD2蛋白表达也较窦性心律者明显增加,MR 分别为右房:1.65±0.72 vs 0.86±0.33(P<0.01);左房:1.72±0.62 vs 0.97±0.37(P<0.05)。11βHSD2分别为右房:-1.18±0.64 vs 0.71+0.21(P<0.01);左房:1.36±0.58 vs 0.85±0.15(P<0.05);但在左右心房之间无论是在窦性心律或心房颤动时,MR 和11βHSD2二者在 mRNA 水平和蛋白表达水平差异均无统计学意义(P>0.05)。结论心房颤动时心房肌组织 MR 和11βHSD2表达增加,醛固酮受体拮抗剂将可能对心房颤动发挥治疗作用。
文摘目的研究小檗碱对胰岛素抵抗模型肝细胞11β-羟基类固醇脱氢酶1（11β-HSD1）mRNA表达的影响。方法应用高浓度胰岛素孵育HepG2细胞24h，建立胰岛素抵抗肝细胞模型。将模型细胞分别置于含不同浓度胰岛素和小檗碱的培养液中培养24h，以葡萄糖氧化酶-过氧化物酶（GOD-POD）法测定培养液中的葡萄糖浓度，计算细胞对葡萄糖的吸收率。应用RT-PCR检测小檗碱作用前后模型细胞11β-HSD1mRNA的表达。结果以含10-7mol／L胰岛素的培养液孵育HepG2细胞24h后，细胞对葡萄糖的吸收明显降低，表明建模成功。模型细胞经高浓度（10μmol／L）小檗碱处理后，葡萄糖吸收率明显增加[（42．53±1．99）％VS（28．16±1．99）％，t=12．9457，P〈0．01]，并且高浓度小檗碱与胰岛素对模型细胞有协同促进葡萄糖吸收的作用。模型细胞11β—HSD 1mRNA表达显著高于非胰岛素抵抗细胞（相对表达量：4．60±0．96 vs 0．67±0．42，t=4．9476，P〈0．05）。经高浓度小檗碱干预24h后，模型细胞11β-HSD1mRNA表达降低，与非胰岛素抵抗HepG2细胞相比差异无统计学意义（相对表达量：1．12±0．35VS0．67±0．42，t=1．1394，P〉0．05）。低浓度（1μmol／L）小檗碱则作用不明显。结论浓度依赖性地下调11β—HSD1mRNA表达是小檗碱改善胰岛素抵抗的作用机制之一。
