Disease relevance of TG

• The inhibitory effect of ANP on Tg mRNA level was reverted in the presence of pertussis toxin, an inhibitor of the G(i)-protein-mediated reduction of the adenylate cyclase activity [1].
• We have characterized two stable transformed mouse cell lines (CG1 and CTG1) that express either the normal vesicular stomatitis virus glycoprotein (G) or a truncated form of the G protein (TG) that lacks the COOH-terminal anchor sequences and is secreted from the cells [2].
• However, neither of the two polymorphisms of candidate genes tested, DGAT1 nor TG, showed a significant (P > 0.10) association with the backfat EBV in the cattle populations examined [3].
• Defective thyroglobulin synthesis and secretion causing goiter and hypothyroidism [4].
• Finally, when bovine serum albumin was substituted for thyroglobulin from each of the patients, iodination of bovine serum albumin was several times greater with the particulate fraction obtained from toxic diffuse goiter tissue than with that obtained from normal tissue [5].

High impact information on TG

• The biosynthesis of thyroid hormones involves an iodinated precursor protein, thyroglobulin, which may be considered an extreme example of a pro-hormone [6].
• However, the efficiency of thyroglobulin as a thyroid hormone precursor is extremely high when the supply of iodine is short; in such conditions, almost all the iodine incorporated is found in iodothyronine [6].
• Thyroglobulin is a dimeric glycoprotein of relative molecular mass (Mr) 660,000 (660K), which is secreted by the thyrocyte and stored in the lumen of the thyroid follicle [6].
• Secretion of hormones results from the endocytosis of thyroglobulin followed by its complete hydrolysis in lysosomes [6].
• Antibodies that specifically bind the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG) were produced in rabbits after injection of a derivative of MOPEG conjugated with bovine thyroglobulin [7].

Chemical compound and disease context of TG

• These results suggest that in vitro iodination of thyroglobulin is increased in toxic diffuse goiter even when patients are made euthyroid by treatment with thionamide drugs as well as when they are given additional T3 for 10 days before operation [5].
• When thyroglobulin and particulate fractions obtained from the same patient were incubated with 125I-, iodide, glucose, and glucose oxidase, the amount of iodine bound to thyroglobulin was several times greater in toxic diffuse goiter than in normal thyroid tissue; administration of T3 did not affect iodination in toxic diffuse goiter [5].
• In adult mice of the transgenic strain TG66.19, in which expression of herpes simplex type 1 virus thymidine kinase (HSVI-TK) is driven in thyrocytes from the thyroglobulin promoter, the drug Ganciclovir causes the death (ablation) of thyrocytes [8].
• We established a thyroglobulin (Tg)-specific, thyroiditis-inducing T-cell clone, B12G, from B6C3F1 mice by the immunization of mouse Tg with lipopolysaccharide (LPS) from Klebsiella strain LEN (O3:K1) [9].

Biological context of TG

• A nonsense mutation causes hereditary goitre in the Afrikander cattle and unmasks alternative splicing of thyroglobulin transcripts [10].
• The hereditary goitre of Afrikander cattle is an autosomal recessive disease characterized in homozygotes by the production of abnormal thyroglobulin (Tg) and the coexistence in the thyroid of normal-sized 8.4-kilobase (kb) Tg mRNA with a misspliced 7.3-kb message having lost exon 9 [10].
• With all these characteristics, the thyroglobulin gene is presented as a paradigm for the analysis of the fate of introns in gene evolution [11].
• It is followed by an open reading frame providing the first data on thyroglobulin primary structure [12].
• We have characterized the glycopeptides contained in a tryptic digest of bovine thyroglobulin in order to establish actual glycosylation sites [13].

Anatomical context of TG

• Immunofluorescence data show an apparent concentration of the TG protein in the rough endoplasmic reticulum [2].
• The effect of thyroglobulin (TG) on binding of TSH to thyroid plasma membranes was studied in vitro [14].
• Except for an immunoreactive product observed in a small portion of the interstitial connective tissue, the location of TG in the lamprey was similar to that in the thyroid of the rat [15].
• Specific adherence of OS lymphocytes to TG-coated beads and of lymphocytes from BSA-immunized chickens to BSA-beads was found [16].
• We have observed that the clearance of thyroglobulin from the circulation occurs in the liver by macrophages [17].

Associations of TG with chemical compounds

• Comparison of the amino terminal sequence of thyroglobulin with that of peptides known to contain thyroid hormones [7,8] demonstrated that the first tyrosine in native thyroglobulin is mainly found as thyroxine in the mature iodinated protein [8] [12].
• While glycosylation was distributed through most of the length of the thyroglobulin sequence, no oligosaccharides containing only mannose and glucosamine were found in the N-terminal half of the molecule [13].
• After 24 h of treatment with the cGMP analogue, N(2),2'-O-dibutyrylguanosine 3':5'-cyclic monophosphate [(Bu)(2)cGMP] (0.1 and 1 mM), an inhibition of iodide uptake and Tg mRNA expression was obtained, evidencing a cGMP-mediated inhibitory signal in the thyroid cell [1].
• TG in isolated globules was highly iodinated (approximately 55 iodine atoms per 12-S TG subunit) suggesting that the covalent nondisulfide cross-linking occurs in part during the iodination of TG and that this process involves the formation of intermolecular dityrosine bridges [18].
• Mechanisms must exist which solubilize or disperse the insoluble luminal content prior to endocytosis of TG [18].

Physical interactions of TG

• Antisera of high avidity were obtained from rabbits that had been injected with AVP coupled to bovine thyroglobulin [19].

Regulatory relationships of TG

• Atrial natriuretic peptide inhibits iodide uptake and thyroglobulin messenger ribonucleic acid expression in cultured bovine thyroid follicles [1].

Other interactions of TG

• A different evolutionary origin of the 5' and 3' regions of the gene is supported by the highly different proportion of exonic material they contain (12% and 3%, respectively) and by the existence of sequence homology between the 3' region of thyroglobulin and acetylcholinesterase [20].
• Allele frequencies of the SNP in TG and CAPN1 were different in this Brahman population than in reported allele frequencies in Bos taurus populations [21].
• Because such isopeptide bridges are generated usually by the action of a transglutaminase, it is reasonable to propose that the covalent polymerization of TG in the globules is under the control of this enzyme [22].
• TSEP-1, TTF-1, and/or Pax-8 are involved in TSH/cAMP-induced negative regulation of the TSH receptor gene in thyrocytes, suppression of MHC class II, and up-regulation of thyroglobulin [23].
• Characterization by affinity cross-linking of a receptor for atrial natriuretic peptide in cultured human thyroid cells associated with reductions in both adenosine 3',5'-monophosphate production and thyroglobulin secretion [24].

Analytical, diagnostic and therapeutic context of TG

• Detailed sequence analysis of the 5' region of the gene and its flanking segment demonstrated that a significant homology exists between bovine and human thyroglobulin sequences, except for the presence within the ruminant promoter region of a 220-base-pair sequence belonging to the bovine monomer repeated family [20].
• Analysis by SDS-gel electrophoresis and immunoblotting confirmed that the protein released by this procedure consisted of TG [18].
• Incubation of TG with TSH did not show an interaction, as assessed by sucrose gradient centrifugation [14].
• By affinity chromatography, two proteins from J774 cells were identified as thyroglobulin-binding proteins with an apparent molecular mass of approximately 33 kD [25].
• The supernates of the homogenates (105,000g) were subjected to sucrose density gradient centrifugation (5--28%) to separate the thyroglobulin fraction [5].

References