Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the growth control of human thyroid cells in different stages of differentiation, we established two human thyroid cell lines of adenomatous goiter and papillary carcinoma. A 59-year-old female patient with adenomatous goiter was operated in September 1991, and a 27-year-old female patient with papillary carcinoma in May 1990. The thyroid cell lines were established by successive passage without cellular or genetic manipulations such as fusing other cell lines or oncogenic viral infection. These cell lines, human adenomatous goiter cells (hAG) and human papillary thyroid carcinoma cells (hPTC), exhibited a flattened polygonal shape and proliferated as a monolayer in cell culture. The doubling time of the hAG cells was 60 h in Ham's F12 medium supplemented with 10% fetal bovine serum, and that of the hPTC cells, 18 h in the same medium. Both cell lines expressed mRNA for TSH receptor and secreted cAMP into the medium during incubation with thyrotropin (TSH) at concentrations as low as 0.01 mU/mL. The effects of activators of protein kinase A (PKA), protein kinase C (PKC), tyrosine kinase (TK), and estradiol (E2) on proliferation of the hAG cells and the hPTC cells were assessed by measuring cellular DNA content in 24-well plates with diaminobenzoic acid. TSH stimulated proliferation of the hAG cells, but it inhibited proliferation of the hPTC cells. Since TSH activates two signaling pathways, the adenyl cyclase-PKA system and phospholipase C-PKC system, we tested effects of dibutylyl cAMP (dBC) and phorbol myristate 13-acetate (PMA), separately. dBC stimulated proliferation of the hAG cells, but it inhibited that of the hPTC cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different growth control of the two human thyroid cell lines of adenomatous goiter and papillary carcinoma. 778 32

Autosomal dominant nonautoimmune hyperthyroidism (ADNAH) is caused by gain of function mutations in the TSH receptor (TSHr) gene and characterized by toxic thyroid hyperplasia with a variable age of onset in the absence of thyroid antibodies and clinical symptoms of autoimmune thyroid disease in at least two generations. We report here a Turkish family with a novel TSHr gene mutation with distinct features all consistent with ADNAH. Thyroid function tests of the proband were as follows: free T3: 13.1 pg/ml (N: 1.8-4.6); free T4: 5.1 ng/dl (N: 0.9-1.7); TSH: 0.01 microIU/ml (N: 0.2-4.2); and TSH receptor antibody: 2 IU/ml (N: 0-10). A heterozygous missense mutation in exon 10 of the TSHr gene (c.1454C>T) resulting in the substitution of valine for alanine at codon 485 (p.Ala485Val) was found in the father and his son and daughter. This mutation had arisen de novo in the father. Functional studies of the novel TSHr germline mutation demonstrated a higher constitutive activation of adenyl cyclase than wild type without any effect on phospholipase C activity. In conclusion, our data indicate that gain of function germline mutations in the TSHr gene should be investigated in families with members suffering from thyrotoxicosis and progressive growth of goiter, but without clinical and biochemical evidence of autoimmune thyroid disease. In addition, patients harboring the same mutation of the TSHr gene may show wide phenotypic variability with respect to the age at onset, and severity of hyperthyroidism and thyroid growth.
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PMID:A family with a novel TSH receptor activating germline mutation (p.Ala485Val). 1817 46

Reactive oxygen species, specifically hydrogen peroxide (H(2)O(2)), have a significant role in hormone production in thyroid tissue. Although recent studies have demonstrated that dual oxidases are responsible for the H(2)O(2) synthesis needed in thyroid hormone production, our data suggest a pivotal role for superoxide dismutase 3 (SOD3) as a major H(2)O(2)-producing enzyme. According to our results, Sod3 is highly expressed in normal thyroid, and becomes even more abundant in rat goiter models. We showed TSH-stimulated expression of Sod3 via phospholipase C-Ca(2+) and cAMP-protein kinase A, a pathway that might be disrupted in thyroid cancer. In line with this finding, we demonstrated an oncogene-dependent decrease in Sod3 mRNA expression synthesis in thyroid cancer cell models that corresponded to a similar decrease in clinical patient samples, suggesting that SOD3 could be used as a differentiation marker in thyroid cancer. Finally, the functional analysis in thyroid models indicated a moderate role for SOD3 in regulating normal thyroid cell proliferation being in line with our previous observations.
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PMID:Extracellular superoxide dismutase is a thyroid differentiation marker down-regulated in cancer. 2057 1

Human thyroid stimulating hormone (TSH) is a glycoprotein secreted by the anterior part of the pituitary gland. TSH plays an important physiological role in the regulation of hypothalamic-pituitary-thyroid axis by modulating the release of the thyroid hormones from the thyroid gland. It induces iodine uptake by the thyroid, promotes thyroid epithelial differentiation and growth, and protects thyroid cells from apoptosis. Impairment of TSH signal transduction pathway leads to thyroid disorders such as goitre, hypothyroidism and hyperthyroidism, which can have complex clinical manifestations. TSH signaling is largely effected through two separate pathways, the adenylate cyclase and the phospholipase C pathways. In spite of its biomedical importance, a concise signaling map of TSH pathway is not available in the public domain. Therefore, we have generated a detailed signaling map of TSH pathway by systematically cataloging the molecular reactions induced by TSH including protein-protein interactions, post-translational modifications, protein translocation events and activation/inhibition reactions. We have cataloged 40 molecular association events, 42 enzyme-substrate reactions and 16 protein translocation events in TSH signaling pathway resource. Additionally, we have documented 208 genes, which are differentially regulated by TSH. We have provided the details of TSH pathway through NetPath (http://www.netpath.org), which is a publicly available resource for human signaling pathways developed by our group. We have also depicted the map of TSH signaling using NetSlim criteria (http://www.netpath.org/netslim/) and provided pathway maps in Wikipathways (http://www.wikipathways.org/). We anticipate that the availability of TSH pathway as a community resource will enhance further biomedical investigations into the function and effects of this important hormone.
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PMID:A Signaling Network of Thyroid-Stimulating Hormone. 2425 51