Thyrotropin regulates tyrosine sulfation of thyroglobulin

Nlend, MC; Cauvi, David M.; Venot, Nicole; Desruisseau, Sylvie; Chabaud, Odile

doi:10.1530/eje.0.1410061

Cited by 17 publications

(11 citation statements)

References 52 publications

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“…Studies in porcine thyrocytes indicate that the stoichiometry of Tg tyrosine sulfation falls in response to TSH stimulation (Nlend et al, 1999b), that in vitro production of thyroid hormone from Tg is decreased when sulfation is inhibited pharmacologically (Nlend et al, 1999a), and that Tyr 5 , a hormonogenic tyrosine residue in porcine Tg, can be tyrosine-sulfated. However, the precise role of Tg tyrosine sulfation in thyroid hormone synthesis remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Early postnatal pulmonary failure and primary hypothyroidism in mice with combined TPST-1 and TPST-2 deficiency

Westmuckett

Hoffhines

Borghei

et al. 2008

General and Comparative Endocrinology

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Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). Tpst double knockouts were generated to investigate the importance of tyrosine sulfation in vivo. Double knockouts were born alive at the expected frequency, were normal in size, and their tissues do not synthesize sulfotyrosine. However, most pups die in the early postnatal period with signs of cardiopulmonary insufficiency. A combination of clinical, magnetic resonance imaging, and histological data indicated that lungs of Tpst double knockouts fail to expand at birth resulting in acute pulmonary hypertension, right-to-left shunting, and death by asphyxia in the early postnatal period. Some double knockouts survive the postnatal period, but fail to thrive and display delayed growth that is due in part to hypothyroidism. In addition, we find that Tpst2−/− mice have primary hypothyroidism, but that Tpst1−/− mice are euthyroid. This suggests that a protein(s) required for thyroid hormone production is sulfated and cannot be sulfated in the absence of TPST-2. Thus, Tpst1 and Tpst2 are the only Tpst genes in mice, tyrosine sulfation is required for normal pulmonary function at birth, and TPST-2 is required for normal thyroid gland function.

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Section: Discussionmentioning

confidence: 99%

Early postnatal pulmonary failure and primary hypothyroidism in mice with combined TPST-1 and TPST-2 deficiency

Westmuckett

Hoffhines

Borghei

et al. 2008

General and Comparative Endocrinology

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“…The fact that tyrosine sulfonation is a common posttranslational modification of thyroglobulin found throughout the vertebrate phylum suggests that it was acquired at an early stage in thyroid evolution (188). Interestingly, it has been demonstrated that TSH down-regulates thyroglobulin sulfonation, particularly on tyrosine residues (189). The biological role of the sulfonated sugars in thyroglobulin (both the terminally capped galactose-3-sulfate as well as the more internally located N-acetylglucosamine-6-sulfate) remains uncertain.…”

Section: B Sulfonation Of Thyroglobulinmentioning

confidence: 99%

“…The biological role of the sulfonated sugars in thyroglobulin (both the terminally capped galactose-3-sulfate as well as the more internally located N-acetylglucosamine-6-sulfate) remains uncertain. It has been speculated that sulfate groups linked to oligosaccharide chains or to tyrosine residues of thyroglobulin might be involved in protein-protein recognition and have implications for the proper folding of thyroglobulin (189). Furthermore, sulfated tyrosines in thyroglobulin may be involved in hormonogenesis, and the control of tyrosine sulfonation by TSH could be related to this process.…”

Section: B Sulfonation Of Thyroglobulinmentioning

confidence: 99%

Sulfonation and Molecular Action

2002

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The sulfonation of endogenous molecules is a pervasive biological phenomenon that is not always easily understood, and although it is increasingly recognized as a function of fundamental importance, there remain areas in which significant cognizance is still lacking or at most minimal. This is particularly true in the field of endocrinology, in which the sulfoconjugation of hormones is a widespread occurrence that is only partially, if at all, appreciated. In the realm of steroid/sterol sulfoconjugation, the discovery of a novel gene that utilizes an alternative exon 1 to encode for two sulfotransferase isoforms, one of which sulfonates cholesterol and the other pregnenolone, has been an important advance. This is significant because cholesterol sulfate plays a crucial role in physiological systems such as keratinocyte differentiation and development of the skin barrier, and pregnenolone sulfate is now acknowledged as an important neurosteroid. The sulfonation of thyroglobulin and thyroid hormones has been extensively investigated and, although this transformation is better understood, there remain areas of incomplete comprehension. The sulfonation of catecholamines is a prevalent modification that has been extensively studied but, unfortunately, remains poorly understood. The sulfonation of pituitary glycoprotein hormones, especially LH and TSH, does not affect binding to their cognate receptors; however, sulfonation does play an important role in their plasma clearance, which indirectly has a significant effect on biological activity. On the other hand, the sulfonation of distinct neuroendocrine peptides does have a profound influence on receptor binding and, thus, a direct effect on biological activity. The sulfonation of specific extracellular structures plays an essential role in the binding and signaling of a large family of extracellular growth factors. In summary, sulfonation is a ubiquitous posttranslational modification of hormones and extracellular components that can lead to dramatic structural changes in affected molecules, the biological significance of which is now beginning to be appreciated.

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“…They are involved in molecular conformation and protein interactions, take part in activation and deactivation of biological activities, and account for much of the negative charge of the Tg molecule (10,30). However, these roles have yet to be fully elucidated and little is known regarding their regulation, although investigators have reported that TSH downregulates Tg sulfation (31).…”

Section: Sulfationmentioning

confidence: 99%

Insights into the posttranslational structural heterogeneity of thyroglobulin and its role in the development, diagnosis, and management of benign and malignant thyroid diseases

Xavier

Maciel

Vieira

et al. 2016

Arch. Endocrinol. Metab.

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Thyroglobulin (Tg) is the major glycoprotein produced by the thyroid gland, where it serves as a template for thyroid hormone synthesis and as an intraglandular store of iodine. Measurement of Tg levels in serum is of great practical importance in the follow-up of differentiated thyroid carcinoma (DTC), a setting in which elevated levels after total thyroidectomy are indicative of residual or recurrent disease. The most recent methods for serum Tg measurement are monoclonal antibody-based and are highly sensitive. However, major challenges remain regarding the interpretation of the results obtained with these immunometric methods, particularly in patients with endogenous antithyroglobulin antibodies or in the presence of heterophile antibodies, which may produce falsely low or high Tg values, respectively. The increased prevalence of antithyroglobulin antibodies in patients with DTC, as compared with the general population, raises the very pertinent possibility that tumor Tg may be more immunogenic. This inference makes sense, as the tumor microenvironment (tumor cells plus normal host cells) is characterized by several changes that could induce posttranslational modification of many proteins, including Tg. Attempts to understand the structure of Tg have been made for several decades, but findings have generally been incomplete due to technical hindrances to analysis of such a large protein (660 kDa). This review article will explore the complex structure of Tg and the potential role of its marked heterogeneity in our understanding of normal thyroid biology and neoplastic processes. Arch Endocrinol Metab. 2016;60(1):66-75

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Thyrotropin regulates tyrosine sulfation of thyroglobulin

Cited by 17 publications

References 52 publications

Early postnatal pulmonary failure and primary hypothyroidism in mice with combined TPST-1 and TPST-2 deficiency

Early postnatal pulmonary failure and primary hypothyroidism in mice with combined TPST-1 and TPST-2 deficiency

Sulfonation and Molecular Action

Insights into the posttranslational structural heterogeneity of thyroglobulin and its role in the development, diagnosis, and management of benign and malignant thyroid diseases

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