Crisp M S, Lane C, Halliwell M, Wynford-Thomas D, Ludgate M
Department of Pathology, University of Wales College of Medicine, Heath Park, Cardiff, UK.
J Clin Endocrinol Metab. 1997 Jun;82(6):2003-5.
Thyroid associated ophthalmopathy (TAO) is generally considered to have an autoimmune pathogenesis but the target antigen has yet to be identified. It is most frequently associated with Graves' disease and there is some logic in assuming that the same antigen, the thyrotropin receptor (TSHR), is the common link. Previous studies, mostly PCR based, aimed at investigating TSHR transcripts in the orbit, have yielded conflicting results, although there is circumstantial evidence for their presence in orbital fat. In this study, we have examined adult human adipose and muscle tissues from various locations, initially by PCR and subsequently by northern blot. We obtained the expected 610bp product in normal intestinal and orbital fat but not skeletal muscle, following two rounds of PCR amplification but only when reverse transcription used a TSHR specific primer. In northern blots, despite loading all of the RNA obtained from total normal orbital fat contents, TSHR transcripts were at the limit of detection and similarly for large samples of intestinal fat. The exception was RNA obtained from TAO orbital fat, in which TSHR transcripts of 4.6 and 1.7kb were clearly visible, as in the thyroid. We conclude that normal adult adipose tissues contain low levels of TSHR transcripts. In TAO, TSHR transcripts are elevated probably due to an increased number of cells, in particular of preadipocytes in orbital adipose tissue.
甲状腺相关眼病(TAO)一般被认为具有自身免疫发病机制,但目标抗原尚未确定。它最常与格雷夫斯病相关,并且假定相同的抗原——促甲状腺素受体(TSHR)是共同联系物存在一定逻辑。以往的研究大多基于PCR,旨在研究眼眶中的TSHR转录本,结果相互矛盾,尽管有间接证据表明其存在于眼眶脂肪中。在本研究中,我们首先通过PCR,随后通过Northern印迹法,检测了来自不同部位的成人人类脂肪和肌肉组织。经过两轮PCR扩增后,我们在正常肠道和眼眶脂肪中获得了预期的610bp产物,但在骨骼肌中未获得,且只有当逆转录使用TSHR特异性引物时才出现该产物。在Northern印迹中,尽管加载了从正常眼眶脂肪总含量中获得的所有RNA,但TSHR转录本处于检测极限,肠道脂肪的大样本情况类似。例外的是从TAO眼眶脂肪中获得的RNA,其中4.6kb和1.7kb的TSHR转录本清晰可见,与甲状腺中的情况一样。我们得出结论,正常成人脂肪组织含有低水平的TSHR转录本。在TAO中,TSHR转录本升高可能是由于细胞数量增加,特别是眼眶脂肪组织中的前脂肪细胞数量增加。