title: A newly identified TSHβ splice variant is involved in the pathology of Hashimoto's thyroiditis.
abstract: Thyrotropin (TSH) is a protein that plays a key role in the control of thyroid function. TSH consists of a common α-subunit and a unique β-subunit; the latter is responsible for hormone specificity. A novel splice variant of human TSHβ was identified in 2009. To date, only the tissue distribution of the human TSHβ splice variant mRNA has been studied. Therefore, we aimed to characterize the protein translated from this splice variant. Salting-out, dialysis and concentration of serum proteins were followed by immunoprecipitation to identify the hTSHβ splice variant in serum. Stable CHO cell lines expressing the hTSHβ splice variant and V5-hTSHα were generated. After co-culture, co-immunoprecipitation was used to determine if the hTSHβ splice variant can dimerise with TSHα. We showed for the first time that the hTSHβ splice variant exists in human serum and dimerises with TSHα. To explore the relationship between the TSHβ splice variant and the pathogenesis of autoimmune thyroiditis, we assessed variations in the mRNA expression of the TSHβ splice variant in the peripheral blood leukocytes (PBLs) of Hashimoto's thyroiditis (HT) patients using quantitative RT-PCR. We found that the mRNA expression levels of the TSHβ splice variant were higher in the PBLs of HT patients who were not undergoing prednisone therapy (n = 10, P < 0.0001) and in the PBLs of HT patients with a longer duration of illness (>18 months) who were undergoing prednisone therapy (n = 5, P = 0.023) than in those of the control group. This pattern was reversed in the PBLs of HT patients with a shorter duration of illness (<9 months) who were undergoing prednisone therapy (n = 8, P < 0.0001). Dexamethasone inhibition of the TSHβ splice variant mRNA expression occurred in a dose- and time-dependent manner. These results demonstrated that the TSHβ splice variant may participate in the pathogenesis of HT.
authors: Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, QiXiangTai Road No22, HePing District, Tianjin 300070, China.
authors: Chunrong
authors: C
authors: Liu
authors: Lanying
authors: L
authors: Li
authors: Fan
authors: F
authors: Ying
authors: Cangdan
authors: C
authors: Xu
authors: Xiaoyi
authors: X
authors: Zang
authors: Zhihong
authors: Z
authors: Gao
mesh_terms: D000328:Adult; D017398:Alternative Splicing / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001483:Base Sequence; D016466:CHO Cells; D016022:Case-Control Studies; D018920:Coculture Techniques; D006224:Cricetinae; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015292:Glycoprotein Hormones, alpha Subunit / Q000378:metabolism; D050031:Hashimoto Disease / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D037322:Thyrotropin, beta Subunit / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D015292:Glycoprotein Hormones, alpha Subunit; D020033:Protein Isoforms; D012333:RNA, Messenger; D037322:Thyrotropin, beta Subunit; D003907:Dexamethasone