Thyroid-Stimulating Hormone: Structure and Function

Magner, James A.

doi:10.1007/978-1-4757-2058-7_4

Cited by 5 publications

(2 citation statements)

References 180 publications

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“…The released T4 becomes effective once converted peripherally to triiodothyronine (T3) by deiodinase enzymes. The functionally active circulating hormones provide a feedback loop directly to both the hypothalamus and the pituitary suppressing further release of TSH and TRH, thereby maintaining homeostatic control of the hypothalamic-pituitary-thyroid axis (Magner 1989, Szkudlinski et al 2002, Sarapura et al 2011.…”

Section: Hormone Structure and Biochemical Detailsmentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: Thyroid-stimulating hormone in thyroid cancer: does it matter?

Nieto¹,

Boelaert²

2016

Endocrine-Related Cancer

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Differentiated thyroid cancer is the most common endocrine malignancy and the incidence is increasing rapidly worldwide. Appropriate diagnosis and post-treatment monitoring of patients with thyroid tumours are critical. Fine needle aspiration cytology remains the gold standard for diagnosing thyroid cancer, and although there have been significant refinements to this technique, diagnostic surgery is often required for patients suspected to have malignancy. Serum thyroid-stimulating hormone (TSH) is higher in patients with malignant thyroid nodules than in those with benign disease, and TSH is proportionally increased in more aggressive tumours. Importantly, we have shown that the pre-operative serum TSH concentration independently predicts the presence of malignancy in subjects presenting with thyroid nodules. Establishing the use of TSH measurements in algorithms identifying high-risk thyroid nodules in routine clinical practice represents an exciting, cost-efficient and non-invasive approach to optimise thyroid cancer diagnosis. Binding of TSH to receptors on thyrocytes stimulates a number of growth promoting pathways both in normal and malignant thyroid cells, and TSH suppression with high doses of levothyroxine is routinely used after thyroidectomy to prevent cancer recurrence, especially in high-risk tumours. This review examines the relationship between serum TSH and thyroid cancer and reflects on the clinical potential of TSH measurements in diagnosis and disease monitoring.

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Section: Hormone Structure and Biochemical Detailsmentioning

confidence: 99%

WOMEN IN CANCER THEMATIC REVIEW: Thyroid-stimulating hormone in thyroid cancer: does it matter?

Nieto¹,

Boelaert²

2016

Endocrine-Related Cancer

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“…TSH is a glycoprotein composed of two noncovalently linked subunits that are synthesized from separate mRNAs {Pierce 1971; Chin, Habener, Kieffer and Maloof 1978;Kourides and Weintraub 1979;Pierce and Parsons 1981;Magner and Weintraub 1986;Magner 1989). The a-subunit has two asparagine-linked oligosaccharide units (Asn 56 and Asn 82), whereas the B-subunit has one (Asn 23).…”

Section: Introductionmentioning

confidence: 99%

Susceptibility to Endoglycosidase F and H at the Individual Glycosylation Sites of Mouse Thyrotropin and Free α-Subunits

Miura¹,

Vs²,

Ja³

1990

Horm Metab Res

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We have studied the differential susceptibility to endoglycosidase F and H of oligosaccharides at the individual glycosylation sites of mouse TSH and free alpha-subunits. Mouse thyrotropic tumor tissue was incubated with D-[2-3H]mannose for 6 h. [3H]Man-labeled TSH and free alpha-subunits were obtained from homogenates using specific antisera and were digested with endoglycosidase F and H in their native states or after heat-denaturation and reduction in the presence of detergents. Tryptic fragments of the digestion products were then analyzed by reverse phase HPLC so that effects of endoglycosidase at the individual glycosylation sites could be determined. There was very little preferential cleavage by endoglycosidase H and F among the glycosylation sites of TSH subunits. Endoglycosidase F treatment of native free alpha-subunits showed slight preferential cleavage at Asn 82 of alpha-subunits after a 4 h incubation, whereas endoglycosidase H cleaved oligosaccharides equally well at Asn 56 and Asn 82. The Asn 82 oligosaccharide of native TSH heterodimers was also slightly preferentially cleaved by endoglycosidase F, but endoglycosidase H cleaved oligosaccharides equally well at all TSH glycosylation sites. Heat denaturation, reduction and the presence of detergent did not alter this slight preferential cleavage by endoglycosidase F at Asn 82 of alpha-subunits, suggesting that the primary structures of the TSH subunits in part influenced the efficiency of enzyme action at specific sites. Thus, the susceptibility to endoglycosidase F differs very slightly at the individual glycosylation sites of mouse TSH and free alpha-subunits, and these small differences could be due to properties of either the enzyme or substrates.

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Characterization of N‐glycans of recombinant human thyrotropin using mass spectrometry

Morelle

Donadio

Ronin

et al. 2005

Rapid Comm Mass Spectrometry

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Thyroid-stimulating hormone is a vital component of the regulatory mechanism that maintains the structure and function of the thyroid gland and governs thyroid hormone release. In this paper we report the first detailed structural characterization of the N-linked oligosaccharides of recombinant human thyroid-stimulating hormone (rhTSH). Using a strategy combining mass spectrometric analysis and sequential exoglycosidase digestion, we have defined the structures of the N-glycans released from recombinant human thyrotropin by peptide N-glycosidase F. All glycans are complex-type glycans and are mainly of the bi- and triantennary type with variable degrees of fucosylation and sialylation. The major non-reducing epitope in the complex-type glycans is: NeuAcalpha2-3Galbeta1-4GlcNAc (sialylated LacNAc). The carbohydrate microheterogeneity at the three glycosylation sites was studied using reversed-phase high-performance liquid chromatography (RP-HPLC), concanavalin A affinity chromatography and mass spectrometric techniques, including both matrix-assisted laser desorption/ionization (MALDI) and electrospray. rhTSH was reduced, carboxymethylated and then digested with trypsin. The mixture of peptides and glycopeptides was subjected to RP-HPLC and the structures of the glycopeptides were determined by MALDI in conjunction with on-target exoglycosidase digestions. After PNGase F digestion, the peptide moiety of the glycopeptide was determined by the presence of the b- and y-series ions derived from its amino acid sequence in the quadrupole time-of-flight tandem mass (QTOF-MS/MS) spectrum. Glycosylation sites Asn-alpha52 and Asn-alpha78 contain mainly bi- and triantennary complex-type glycans. Only glycosylation site Asn-alpha52 bears fucosylated N-glycans. Minor tetraantennary complex structures were also observed on both glycosylation sites. Profiling of the carbohydrate moieties of Asn-beta23 indicates a large heterogeneity. Bi-, tri-, and tetraantennary N-glycans were present at this site. These data demonstrate site-specificity of glycosylation in the alpha subunit but not in the beta subunit of rhTSH with Asn-alpha52 bearing essentially di- and triantennary glycans with or without core fucosylation and bi- and triantennary glycans with no core fucosylation being attached to Asn-alpha78.

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Thyroid-Stimulating Hormone: Structure and Function

Cited by 5 publications

References 180 publications

WOMEN IN CANCER THEMATIC REVIEW: Thyroid-stimulating hormone in thyroid cancer: does it matter?

WOMEN IN CANCER THEMATIC REVIEW: Thyroid-stimulating hormone in thyroid cancer: does it matter?

Susceptibility to Endoglycosidase F and H at the Individual Glycosylation Sites of Mouse Thyrotropin and Free α-Subunits

Characterization of N‐glycans of recombinant human thyrotropin using mass spectrometry

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