Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spontaneous hypothyroidism was developed in two patients with Graves' hyperthyroidism 1.8 or 1 years after antithyroid drug therapy. In these patients anti-thyrotropin (TSH) receptor antibodies were detected. Thyrotropin receptor antibody (TRAb) index measured with TSH radioreceptor assay was 61.0% in case 1 and 68.0% in case 2 (normal value: -10 to 10%), and human thyroid adenylate cyclase stimulating activities (HTACS) were 154% in case 1 and 190% in case 2 (normal value: 70 to 130%). IgG from case 1 suppressed the stimulating activity of bovine TSH (bTSH) on thyroid adenylate cyclase in low concentrations in vitro. These results indicate that a blocking type of anti-TSH receptor antibodies as well as concomitant chronic thyroiditis might be a causative factor in patients who developed spontaneous hypothyroidism shortly after the cessation of antithyroid drugs.
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PMID:Characteristics of anti-TSH receptor antibodies in two patients who developed spontaneous hypothyroidism after antithyroid drug therapy for hyperthyroid Graves' disease. 366 Apr 1

Thyroperoxidase-catalyzed iodination of thyroglobulin and subsequent oxidative coupling of iodinated tyrosyl residues to protein-bound iodothyronines are the key reactions in thyroid hormone biosynthesis. Under sufficient iodine supply, both synthesis steps are rate-limited by the availability of hydrogen peroxide (H(2)O(2)), which is required as final electron acceptor. The primary enzyme feeding H(2)O(2) to thyroid peroxidase is a heterodimeric NADPH oxidase complex of dual oxidase 2 (DUOX2) and DUOX maturation factor 2 (DUOXA2) at the apical plasma membrane. While the thyrotropin receptor mediates most biological effects through the Gs/adenyl cyclase/cAMP pathway, the Gq/phospholipase C-beta cascade induces H(2)O(2) generation via synergistic effects of increased intracellular calcium and protein kinase C activation on DUOX2/DUOXA2. Defects in thyroidal H(2)O(2) generation have been identified in a subset of patients with congenital hypothyroidism. These include loss-of-function mutations in DUOX2 and DUOXA2. Thyrotropin receptor mutations with preferential loss of Gq-coupling may indirectly affect H(2)O(2) production. Expressivity of the defects can be highly variable owning to the presence of genetic modifiers (e.g., the paralogs DUOX1 and DUOXA1), and environmental factors particularly nutritional iodide intake.
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PMID:Defects of thyroidal hydrogen peroxide generation in congenital hypothyroidism. 2012 87