Tollet-Egnell P, Flores-Morales A, Stavréus-Evers A, Sahlin L, Norstedt G
Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
Endocrinology. 1999 Aug;140(8):3693-704. doi: 10.1210/endo.140.8.6878.
The SOCS (suppressors of cytokine signaling) proteins have been suggested to function as inhibitors of cytokine receptor signaling. We have analyzed SOCS-2, SOCS-3, and CIS expression in relation to GH actions in the rat. SOCS-2, SOCS-3, and CIS transcripts were detected in various GH responsive tissues, including liver, muscle, and fat. In addition to the finding that different tissues express different levels of SOCS-2, SOCS-3, and CIS messenger RNA (mRNA), the steady-state levels of these SOCS transcripts were dependent on the endocrine status of the animal. SOCS-3 expression was 5-fold higher in fat from old compared with younger rats. Hypophysectomy reduced the levels of SOCS-2 and CIS mRNA in liver, muscle, and fat, whereas SOCS-3 expression was unchanged. Using primary cultures of rat hepatocytes, GH was shown to increase SOCS-2, SOCS-3, and CIS mRNA levels with different kinetics. SOCS-3 was rapidly and transiently induced, whereas SOCS-2 and CIS were increased in a slower fashion. Glucocorticoids blocked GH-induced SOCS-3 expression in cultured hepatocytes, whereas SOCS-2 and CIS expression was potentiated. Our data fit well with a concept of SOCS proteins acting as modulators of GH signal transduction.
细胞因子信号转导抑制因子（SOCS）蛋白被认为可作为细胞因子受体信号转导的抑制剂。我们分析了SOCS-2、SOCS-3和CIS在大鼠体内与生长激素（GH）作用相关的表达情况。在包括肝脏、肌肉和脂肪在内的各种GH反应性组织中检测到了SOCS-2、SOCS-3和CIS转录本。除了不同组织表达不同水平的SOCS-2、SOCS-3和CIS信使核糖核酸（mRNA）这一发现外，这些SOCS转录本的稳态水平还取决于动物的内分泌状态。与年轻大鼠相比，老年大鼠脂肪中的SOCS-3表达高5倍。垂体切除降低了肝脏、肌肉和脂肪中SOCS-2和CIS mRNA的水平，而SOCS-3的表达未发生变化。利用原代培养的大鼠肝细胞，研究表明GH可通过不同的动力学增加SOCS-2、SOCS-3和CIS mRNA的水平。SOCS-3被快速短暂诱导，而SOCS-2和CIS则以较慢的方式增加。糖皮质激素可阻断培养肝细胞中GH诱导的SOCS-3表达，而SOCS-2和CIS的表达则增强。我们的数据与SOCS蛋白作为GH信号转导调节剂的概念非常吻合。
