Division of Endocrinology, Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, STOP 9410, Lubbock, Texas 79430-9410, USA.
Eur J Endocrinol. 2010 Nov;163(5):765-73. doi: 10.1530/EJE-10-0376. Epub 2010 Aug 24.
Non-thyroidal illness syndrome (NTIS) is related to changes in thyroid hormone (TH) physiology. Skeletal muscle (SM) plays a major role in metabolism, and TH regulates SM phenotype and metabolism. We aimed to characterize the SM of non-septic shock NTIS patients in terms of: i) expression of genes and proteins involved in TH metabolism and actions; and ii) NFKB's pathway activation, a responsible factor for some of the phenotypic changes in NTIS. We also investigated whether the patient's serum can induce in vitro the effects observed in vivo.
Serum samples and SM biopsies from 14 patients with non-septic shock NTIS and 11 controls. Gene and protein expression and NFKB1 activation were analyzed by quantitative PCR and immunoblotting. Human SM cell (HSkMC) cultures to investigate the effects of patient's serum on TH action mediators.
Patients with non-septic shock NTIS showed higher levels of pro-inflammatory cytokines than controls. Expression of TRβ (THRB), TRα1 (THRA), and retinoid X receptor γ (RXRG) was decreased in NTIS patients. RXRA gene expression was higher, but its protein was lower in NTIS than controls, suggesting the existence of a post-transcriptional mechanism that down-regulates protein levels. NFKB1 pathway activation was not different between NTIS and control patients. HSkMC incubated with patient's serum increased TH receptor and RXRG gene expression after 48 h.
Patients with non-septic shock NTIS showed decreased expression of TH receptors and RXRs, which were not related to increased activation of the NFKB1 pathway. These findings could not be replicated in cultures of HSkMCs incubated in the patient's serum.
非甲状腺疾病综合征（NTIS）与甲状腺激素（TH）生理变化有关。骨骼肌（SM）在代谢中起主要作用，TH 调节 SM 表型和代谢。我们旨在从以下两个方面描述非脓毒性休克 NTIS 患者的 SM：i）参与 TH 代谢和作用的基因和蛋白的表达；ii）NFKB 途径的激活，这是 NTIS 中一些表型变化的一个负责因素。我们还研究了患者的血清是否可以在体外诱导体内观察到的作用。
从 14 例非脓毒性休克 NTIS 患者和 11 例对照中采集血清样本和 SM 活检。通过定量 PCR 和免疫印迹分析基因和蛋白表达以及 NFKB1 激活。进行人 SM 细胞（HSkMC）培养以研究患者血清对 TH 作用介质的影响。
与对照组相比，非脓毒性休克 NTIS 患者的促炎细胞因子水平更高。TRβ（THRB）、TRα1（THRA）和视黄酸 X 受体γ（RXRG）的表达在 NTIS 患者中降低。NTIS 患者的 RXRA 基因表达较高，但蛋白水平较低，表明存在一种转录后机制下调蛋白水平。NTIS 和对照患者之间的 NFKB1 途径激活没有差异。用患者的血清孵育 HSkMC 后，48 小时后 TH 受体和 RXRG 基因表达增加。
非脓毒性休克 NTIS 患者表现出 TH 受体和 RXR 的表达降低，这与 NFKB1 途径的激活增加无关。这些发现不能在培养的 HSkMC 中用患者的血清复制。
