Otto E, Förster G, Kuhlemann K, Hansen C, Kahaly G J
Department of Medicine III, Johannes Gutenberg, University Hospital, Mainz, Germany.
Clin Exp Rheumatol. 1996 May-Jun;14 Suppl 15:S77-84.
The human thyrotropin receptor (hTSHR) is a potential common antigen in endocrine autoimmunity. Recently, some studies demonstrated transcripts for hTSHR or its components in the extrathyroidal tissue of patients with autoimmune thyroid disease (ATD), although others were unable to confirm these findings. In the present study we investigated orbital adipose/connective and muscle tissue as well as primary cell cultures of orbital fibroblasts and myoblasts from patients with thyroid and eye disease.
The messenger ribonucleic acid (mRNA) of hTSHR was reverse transcribed and amplified by polymerase chain reaction (PCR). To evaluate the existence of a functional hTSHR in cultured orbital fibroblasts and muscle cells, the TSH-mediated metabolic activity of the cells was measured by tetrazolium assay.
We were unable to amplify the extracellular domain of hTSHR regardless of the material used. In contrast, transcripts of the transmembrane and intracellular domain of hTSHR were detectable in both crude retrobulbar tissue and primary cells cultures. The results of fibroblast amplification experiments were more successful than those with myoblasts. Furthermore, we were able to confirm that these transcripts of hTSHR can also be detected in the retro-ocular tissue of healthy persons. Independently of the TSH activity employed, no stimulation of fibroblasts or myoblasts was detected, even at higher TSH levels.
These data do not suggest that hTSHR is expressed in a functional form in orbital tissue. However, a part of the receptor could play a role in the pathogenesis of autoimmune eye disease as a non-functional but antigenic protein. Whether a common antigen in the thyroid and orbit is related to hTSHR has not been clarified yet.
人促甲状腺激素受体(hTSHR)是内分泌自身免疫中一种潜在的共同抗原。最近,一些研究证明了自身免疫性甲状腺疾病(ATD)患者甲状腺外组织中有hTSHR或其组分的转录本,尽管其他研究未能证实这些发现。在本研究中,我们调查了患有甲状腺和眼部疾病患者的眼眶脂肪/结缔组织和肌肉组织,以及眼眶成纤维细胞和平滑肌细胞的原代细胞培养物。
通过聚合酶链反应(PCR)对hTSHR的信使核糖核酸(mRNA)进行逆转录和扩增。为了评估培养的眼眶成纤维细胞和肌肉细胞中功能性hTSHR的存在,通过四氮唑测定法测量细胞的促甲状腺激素(TSH)介导的代谢活性。
无论使用何种材料,我们均无法扩增hTSHR的细胞外结构域。相比之下,在球后粗组织和原代细胞培养物中均可检测到hTSHR跨膜和细胞内结构域的转录本。成纤维细胞扩增实验的结果比成肌细胞的更成功。此外,我们能够证实在健康人的眼后组织中也能检测到这些hTSHR转录本。无论采用何种TSH活性,即使在较高的TSH水平下,也未检测到对成纤维细胞或成肌细胞的刺激。
这些数据并不表明hTSHR在眼眶组织中以功能形式表达。然而,该受体的一部分可能作为一种无功能但具有抗原性的蛋白质,在自身免疫性眼病的发病机制中起作用。甲状腺和眼眶中的共同抗原是否与hTSHR相关尚未明确。