Kumar Seema, Coenen Michael J, Scherer Philipp E, Bahn Rebecca S
Division of Pediatric Endocrinology, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Clin Endocrinol Metab. 2004 Feb;89(2):930-5. doi: 10.1210/jc.2003-031427.
The signs and symptoms of Graves' ophthalmopathy (GO) result from increased volume of the orbital contents, including adipose, connective, and extraocular muscle tissues. We wanted to determine whether the expanded adipose tissue volume might be in part attributable to de novo adipogenesis. We measured levels of mRNA encoding leptin, adiponectin, peroxisome proliferator-activated receptor gamma (PPAR gamma), preadipocyte factor-1, and TSH receptor (TSHr) genes in orbital adipose tissues from GO patients (n = 22) and normal individuals (n = 18) and in orbital preadipocyte cultures derived from GO patients (n = 6) and normal subjects (n = 3) using quantitative real-time RT PCR. We found increased leptin, adiponectin, PPAR gamma, and TSHr expression in GO compared with normal orbital tissue samples, with positive correlations in the GO tissues between TSHr and leptin, adiponectin and PPAR gamma. In vitro differentiation of GO and normal preadipocytes resulted in enhanced adiponectin, leptin, and TSHr expression, with greater expression of the latter two genes in the GO cultures. These results suggest that de novo adipogenesis within orbital tissues with parallel enhanced expression of TSHr may be important in the pathogenesis of GO, and that potential therapies for GO might include inhibition of the adipogenic pathway.
格雷夫斯眼病（GO）的体征和症状源于眼眶内容物体积增加，包括脂肪、结缔组织和眼外肌组织。我们想确定眼眶脂肪组织体积的增加是否部分归因于脂肪新生。我们使用定量实时逆转录聚合酶链反应（RT-PCR），检测了GO患者（n = 22）和正常个体（n = 18）眼眶脂肪组织以及GO患者（n = 6）和正常受试者（n = 3）眼眶前脂肪细胞培养物中编码瘦素、脂联素、过氧化物酶体增殖物激活受体γ（PPARγ）、前脂肪细胞因子-1和促甲状腺激素受体（TSHr）基因的mRNA水平。我们发现，与正常眼眶组织样本相比，GO患者眼眶组织中瘦素、脂联素、PPARγ和TSHr的表达增加，且GO组织中TSHr与瘦素、脂联素与PPARγ之间呈正相关。GO和正常前脂肪细胞的体外分化导致脂联素、瘦素和TSHr表达增强，后两个基因在GO培养物中的表达更高。这些结果表明，眼眶组织内的脂肪新生以及TSHr表达的平行增强可能在GO的发病机制中起重要作用，并且GO的潜在治疗方法可能包括抑制脂肪生成途径。
