Itoh Emina, Iida Keiji, Kim Dong-Sun, Del Rincon Juan P, Coschigano Karen T, Kopchick John J, Thorner Michael O
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Box 800466, Charlottesville, VA 22908, USA.
Growth Horm IGF Res. 2004 Dec;14(6):462-6. doi: 10.1016/j.ghir.2004.07.002.
11Beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) is expressed in several tissues and converts inactive glucocorticoids (GC) to active GC. 11betaHSD1 activity, evaluated by urine cortisol metabolites, is increased in patients with hypopituitarism and decreased by GH replacement. Skeletal muscle wasting is one of the major characteristics of GH deficiency (GHD). We hypothesized that increased 11betaHSD1 activity and increased GC action in skeletal muscle may play a role in the development of muscle atrophy observed in GHD patients. Glutamine synthetase (GS) mRNA in muscle has been reported to be related to GC-induced muscle atrophy. In this study, we measured mRNA levels of 11betaHSD1 and GS in skeletal muscle of GH receptor gene disrupted (GHR-/-) mice and of their age-matched wild-type mice controls to elucidate the physiological significance of 11betaHSD1 and GC in the development of GHD-associated muscle atrophy in vivo. We also measured the expression of these genes in hypertrophied muscles of giant, bovine GH transgenic mice. In skeletal muscle, although IGF-I mRNA levels were decreased in GHR-/- mice, 11betaHSD1 mRNA levels were not significantly changed compared to wild-type mice. In addition, expression level of 11betaHSD1 in muscle was lower compared to that seen in liver. GS mRNA in skeletal muscle of GHR-/- mice was not significantly different from that of controls. In bGH mice, 11betaHSD1 and GS mRNA levels were not altered compared to control mice. These data do not support a significant role of 11betaHSD1 and GC action in skeletal muscle in the development of muscle atrophy associated with GHD.
11β-羟基类固醇脱氢酶1（11β-HSD1）在多种组织中表达，并将无活性的糖皮质激素（GC）转化为活性GC。通过尿皮质醇代谢产物评估的11βHSD1活性在垂体功能减退患者中升高，而生长激素替代治疗可使其降低。骨骼肌萎缩是生长激素缺乏症（GHD）的主要特征之一。我们推测，骨骼肌中11βHSD1活性增加和GC作用增强可能在GHD患者肌肉萎缩的发生中起作用。据报道，肌肉中的谷氨酰胺合成酶（GS）mRNA与GC诱导的肌肉萎缩有关。在本研究中，我们测量了生长激素受体基因敲除（GHR-/-）小鼠及其年龄匹配的野生型对照小鼠骨骼肌中11βHSD1和GS的mRNA水平，以阐明11βHSD1和GC在体内GHD相关肌肉萎缩发生中的生理意义。我们还测量了巨型牛生长激素转基因小鼠肥大肌肉中这些基因的表达。在骨骼肌中，虽然GHR-/-小鼠的IGF-I mRNA水平降低，但与野生型小鼠相比，11βHSD1 mRNA水平没有显著变化。此外，肌肉中11βHSD1的表达水平低于肝脏中的表达水平。GHR-/-小鼠骨骼肌中的GS mRNA与对照组无显著差异。在bGH小鼠中，与对照小鼠相比，11βHSD1和GS mRNA水平没有改变。这些数据不支持11βHSD1和GC作用在骨骼肌中对与GHD相关的肌肉萎缩发展起显著作用。
