Glycosylation in the Thyroid Gland: Vital Aspects of Glycoprotein Function in Thyrocyte Physiology and Thyroid Disorders

Ząbczyńska, Marta; Kozłowska, Kamila; Pocheć, Ewa

doi:10.3390/ijms19092792

Cited by 48 publications

(67 citation statements)

References 144 publications

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“…The polypeptide chain of the human Tg molecule contains 20 putative N-linked glycosylation sites, of which 16 are glycosylated in the mature Tg molecule (36,37). Sialylation is a late post-translational modification of human Tg.…”

Section: Gwas Of Thyroglobulin Levels 889mentioning

confidence: 99%

Genetic Variants in theST6GAL1Gene Are Associated with Thyroglobulin Plasma Level in Healthy Individuals

Matana

Popović

Boutin

et al. 2019

Thyroid

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Background: Thyroglobulin (Tg) is a 660 kDa iodoglycoprotein that serves as a scaffold for thyroid hormone synthesis. Although a twin study showed that variability of serum Tg levels has a substantial genetic basis, no genome-wide association study (GWAS) of serum/plasma Tg levels has been performed to date. The aim of this study was to identify genetic variants associated with plasma Tg levels among healthy individuals. Methods: A GWAS was conducted on two Croatian cohorts, and a combined analysis was performed. The analyses included 1094 individuals. A total of 7,597,379 variants, imputed using the 1000 Genomes reference panel, were analyzed for association. GWAS was performed under an additive model, controlling for age, sex, and relatedness within each data set. Combined analysis was conducted using the inverse-variance fixed-effects method. Results: Sixteen variants located on chromosome 3, within the ST6GAL1 gene, reached genome-wide significance. The lead SNP was rs4012172 (p ¼ 1:29 • 10 À 10), which explained 3.19% of the variance in Tg levels. ST6GAL1 belongs to the sialyltransferase protein family, which has a fundamental role in the synthesis of specific sialylated structures on various glycoproteins, including Tg. It is known that only immature Tg (poorly sialylated or desialylated) can be transferred to the bloodstream. Conclusions: A highly biologically plausible locus was identified that could have a role in the regulation of plasma Tg levels in healthy individuals.

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Section: Gwas Of Thyroglobulin Levels 889mentioning

confidence: 99%

Genetic Variants in theST6GAL1Gene Are Associated with Thyroglobulin Plasma Level in Healthy Individuals

Matana

Popović

Boutin

et al. 2019

Thyroid

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“…It is well known that glycosylation plays a significant role in tumour progression, metastasis, and immune modulation of various types of cancers, including thyroid carcinomas [3,73]. The contribution of glycosylation changes to disease progress was shown also in autoimmunity processes [66], among others those taking place in the thyroid gland [72,75]. It was hypothesised that TSHR glycans are involved in breaking the self-tolerance state in GD [57].…”

Section: Resultsmentioning

confidence: 99%

“…logicznej różnych typów nowotworów, w tym guzów tarczycy [3,73]. Udział zmian glikozylacji w postępie choroby wykazano również w procesach autoimmunizacyjnych [66], między innymi w gruczole tarczowym [72,75]. Postawiono hipotezę, zgodnie z którą glikany TSHR biorą udział w przełamywaniu stanu tolerancji w GD [57].…”

Section: Prace Poglądoweunclassified

Glycosylation of thyroid-stimulating hormone receptor

Korta

Pocheć

2019

Endokrynologia Polska

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Thyroid-stimulating hormone receptor (TSHR) is a typical membrane receptor with 7-transmembrane helix domain (7TMR), coupled to the G protein. The mature receptor, present in the cell membrane, is composed of the A subunit comprising a large extracellular domain, and the B subunit, which consists of a short extracellular fragment anchored in the cell membrane and an intracellular part. The TSH receptor is subject to numerous post-translational modifications that determine its final structure and significantly affect its activity. One of them is glycosylation. TSHR is abundantly N-glycosylated, due to the presence of six N-glycosylation sites in the extracellular domain (Asn77, Asn99, Asn113, Asn177, Asn198, Asn302), mostly evolutionarily conserved. N-glycans constitute 30-40% of the receptor molecular weight. The glycans are necessary for the receptor trafficking to the plasma membrane and binding of TSH to the receptor. Fucosylated and sialylated N-oligosaccharides were found on TSHR molecules. The increased sialylation of TSHR glycans correlates positively with the receptor binding ability and prolongs the time of receptor incorporation into the cell membrane. TSHR is the main autoantigen in Graves' disease (GD), one of the thyroid autoimmune diseases. One hypothesis assumes that the higher N-glycosylation of THSR in human compared to animals influences the breaking of autotolerance and GD development. N-oligosaccharides are the important part of THSR molecule, necessary for the proper functioning of receptors and probably involved in thyroid autoimmunity in GD.

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“…Thyroid dysfunction is primarily diagnosed by the levels of thyroid stimulating hormone (TSH), a regulator of TH production. However, bioactivity of TSH is related to glycosylation modi cations and age [39]; current clinical assays do not distinguish between TSH glycosylated forms. The expression of varied modi ed TSH protein in the aged population may account for discrepancies in diagnosis and prevalence observed in studies of aging patients, emphasizing the need for identifying other diagnostic targets.…”

Section: Discussionmentioning

confidence: 99%

Sex Impacts Cardiac Function and the Proteome Response to Thyroid Hormone in Aged Mice

Zhu¹,

Olson²,

Portman³

et al. 2020

Preprint

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Background Sex and age have substantial influence on thyroid function. Sex influences the risk and clinical expression of thyroid disorders (TDs), with age a proposed trigger for the development of TDs. Cardiac function is affected by thyroid hormone levels with gender differences. Accordingly, we investigated the proteomic changes involved in sex based cardiac responses to thyroid dysfunction in elderly mice. Methods Aged (18–20 months) male and female C57BL/6 mice were fed diets to create euthyroid, hypothyroid, or hyperthyroid states. Serial echocardiographs were performed to assess heart function. Proteomic changes in cardiac protein profiles were assessed by 2-D DIGE and LC-MS/MS, and a subset confirmed by immunoblotting. Results Serial echocardiographs showed ventricular function remained unchanged regardless of treatment. Heart rate and size increased (hyperthyroid) or decreased (hypothyroid) independent of sex. Pairwise comparison between the six groups identified 55 proteins (≥ 1.5-fold difference and p < 0.1). Compared to same-sex controls 26/55 protein changes were in the female hypothyroid heart, whereas 15/55 protein changes were identified in the male hypothyroid, and male and female hyperthyroid heart. The proteins mapped to oxidative phosphorylation, tissue remodeling and inflammatory response pathways. Conclusion We identified both predicted and novel proteins with gender specific differential expression in response to thyroid hormone status, providing a catalogue of proteins associated with thyroid dysfunction. Pursuit of these proteins and their involvement in cardiac function will expand our understanding of mechanisms involved in sex-based cardiac response to thyroid dysfunction.

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Glycosylation in the Thyroid Gland: Vital Aspects of Glycoprotein Function in Thyrocyte Physiology and Thyroid Disorders

Cited by 48 publications

References 144 publications

Genetic Variants in theST6GAL1Gene Are Associated with Thyroglobulin Plasma Level in Healthy Individuals

Genetic Variants in theST6GAL1Gene Are Associated with Thyroglobulin Plasma Level in Healthy Individuals

Glycosylation of thyroid-stimulating hormone receptor

Sex Impacts Cardiac Function and the Proteome Response to Thyroid Hormone in Aged Mice

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