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Open access

Ying Sun, Di Teng, Lei Zhao, Xiaoguang Shi, Yongze Li, Zhongyan Shan, and Weiping Teng

Objective

Central sensitivity of thyroid hormone refers to the sensitivity of hypothalamic–pituitary–thyroid (HPT) axis to the change in circulating free thyroxine (fT4). A complex relationship exists between thyroxine levels and iodine nutritional status. To explore the relationship between thyroid hormone sensitivity and iodine nutritional status in elevated thyrotropin (TSH), we used national data to assess the relationship between thyroid hormone sensitivity and iodine nutritional status with contrasting demographic characteristics in China.

Methods

We enrolled 12,197 participants with TSH > 4.2 mIU/L from China. Serum and urine samples were collected, and we measured serum fT4, TSH, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) levels and urinary iodine concentration (UIC). The thyroid hormone sensitivity indices were calculated based on fT4 and TSH. The thyroid feedback quantile-based index (TFQI) is a new index to reflect thyroid hormone sensitivity. Higher TFQI quartiles indicated lower thyroid hormone sensitivity.

Results

The odds ratios (ORs) for the fourth versus first TFQI quartile were 0.84 (95% CI 0.72–0.99) for iodine deficiency, 1.24 (95% CI 1.05–1.47) for TPOAb+, and 0.44 (95% CI 0.40–0.50) for females. The OR of the fourth and first TFQI quartiles for age <30 years and >60 years was 2.09 (95% CI 1.82–2.41) and 1.19 (95% CI 1.05–1.36), respectively (P  < 0.05). Other thyroid sensitivity indices also yielded similar results.

Conclusion

Thyroid hormone sensitivity and age have a U-shaped association in individuals with elevated TSH. Increased thyroid hormone sensitivity is associated with iodine deficiency and the female gender. Decreased thyroid hormone sensitivity is associated with TPOAb+. These findings are interesting and potentially useful for understanding the interaction between iodine nutrition and the hypothalamic–pituitary–thyroid axis.

Open access

Yingxin Fang, Pingping Dang, Yue Liang, Defa Zhao, Ranran Wang, Yue Xi, Dan Zhang, Wei Wang, Zhongyan Shan, Weiping Teng, and Xiaochun Teng

Background

Proper thyroid hormone signaling via the TRα1 nuclear receptor is required for normal neurodevelopmental processes. The specific downstream mechanisms mediated by TRα1 that impact brain development remain to be investigated.

Methods

In this study, the structure, function and transcriptome of hippocampal tissue in a mouse model expressing the first RTHα mutation discovered in a patient, THRA E403X, were analyzed. RNAscope was used to visualize the spatial and temporal expression of Thra1 mRNA in the hippocampus of WT mice, which is corresponding to THRA1 mRNA in humans. The morphological structure was analyzed by Nissl staining, and the synaptic transmission was analyzed on the basis of long-term potentiation. The Morris water maze test and the zero maze test were used to evaluate the behavior. RNA-seq and quantitative real-time PCR were used to analyze the differentially expressed genes (DEGs) of the hippocampal tissues in the mouse model expressing the Thra E403X mutation.

Results

The juvenile mutant Thra E403X mice presented with delayed neuronal migration, disordered neuronal distribution, and decreased synaptic plasticity. A total of 754 DEGs, including 361 upregulated genes and 393 downregulated genes, were identified by RNA-seq. DEG-enriched Gene Ontology (GO) and KEGG pathways were associated with PI3K-Akt signaling, ECM−receptor interaction, neuroactive ligand−receptor interaction, and a range of immune-related pathways. 25 DEGs were validated by qPCR.

Conclusions

The Thra E403X mutation results in histological and functional abnormalities, as well as transcriptomic alterations in the juvenile mouse hippocampus. This study of the Thra E403X mutant offers new insights into the biological cause of RTHα-associated neurological diseases.