科研之友
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摘要
Thyrotropin (TSH) is a protein that plays a key role in the control of thyroid function. TSH consists of a common alpha-subunit and a unique beta-subunit; the latter is responsible for hormone specificity. A novel splice variant of human TSH beta was identified in 2009. To date, only the tissue distribution of the human TSH beta 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 hTSH beta splice variant in serum. Stable CHO cell lines expressing the hTSH beta splice variant and V5-hTSH alpha were generated. After co-culture, co-immunoprecipitation was used to determine if the hTSH beta splice variant can dimerise with TSH alpha. We showed for the first time that the hTSH beta splice variant exists in human serum and dimerises with TSH alpha. To explore the relationship between the TSH beta splice variant and the pathogenesis of autoimmune thyroiditis, we assessed variations in the mRNA expression of the TSH beta 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 TSH beta 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 TSH beta splice variant mRNA expression occurred in a dose- and time-dependent manner. These results demonstrated that the TSH beta splice variant may participate in the pathogenesis of HT.
- 出版日期2012-12
- 单位天津医科大学
