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Article: Activation of the thyroid peroxidase gene in human thyroid cells: Effect of thyrotrophin, forskolin and phorbol ester

TitleActivation of the thyroid peroxidase gene in human thyroid cells: Effect of thyrotrophin, forskolin and phorbol ester
Authors
Issue Date1989
PublisherSociety for Endocrinology. The Journal's web site is located at http://jme.endocrinology-journals.org/
Citation
Journal Of Molecular Endocrinology, 1989, v. 3 n. 1, p. 1-5 How to Cite?
AbstractThe enzyme thyroid peroxidase (TPO) plays a central role in thyroid hormone synthesis and is the target for the autoimmune attack in lymphocytic thyroiditis. We have examined the activation of the TPO gene in cultured human thyrocytes using slot blot hybridization with a synthetic 40 mer oligonucleotide probe derived from the nucleotide sequence of the human TPO gene. The oligonucleotide probe was shown by Northern blotting to hybridize specifically to an approximately 3 kb RNA species from thyroid tissue of patients with Graves' disease, but not to RNA preparations from human or bovine retinal tissue, providing compelling evidence for the specificity of the probe for TPO mRNA. Addition of TSH (10 U/ml) to primary thyroid cultures for 4h led to increased TPO mRNA levels which were maximal after 48 h and significantly higher than basal even after 7 days of co-culture. Activation of TPO mRNA by TSH showed dose dependency over a wide range (0.01-100 mU/ml), with a maximal effect at 10 mU TSH/ml in cells cultured for a period of 72 h. Comparison of TPO mRNA levels with the accumulation of thyroglobulin mRNA levels following stimulation by TSH indicated that the induction of the gene encoding thyroglobulin precedes transcription of the TPO gene. The adenylate cyclase activator forskolin (1-100 μM) mimicked TSH in increasing TPO mRNA levels whilst, in contrast, the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA; 0.01-1 μM) led to levels of TPO mRNA that were lower than basal. Thus TSH induces a specific dose-dependent activation of TPO mRNA which is mimicked by agents which increase cyclic AMP. In contrast, TPA-induced activation of protein kinase C inhibits this response.
Persistent Identifierhttp://hdl.handle.net/10722/161780
ISSN
2015 Impact Factor: 2.947
2015 SCImago Journal Rankings: 1.674
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCollison, KSen_US
dc.contributor.authorBanga, JPen_US
dc.contributor.authorBarnett, PSen_US
dc.contributor.authorKung, AWCen_US
dc.contributor.authorMcgregor, AMen_US
dc.date.accessioned2012-09-05T05:14:53Z-
dc.date.available2012-09-05T05:14:53Z-
dc.date.issued1989en_US
dc.identifier.citationJournal Of Molecular Endocrinology, 1989, v. 3 n. 1, p. 1-5en_US
dc.identifier.issn0952-5041en_US
dc.identifier.urihttp://hdl.handle.net/10722/161780-
dc.description.abstractThe enzyme thyroid peroxidase (TPO) plays a central role in thyroid hormone synthesis and is the target for the autoimmune attack in lymphocytic thyroiditis. We have examined the activation of the TPO gene in cultured human thyrocytes using slot blot hybridization with a synthetic 40 mer oligonucleotide probe derived from the nucleotide sequence of the human TPO gene. The oligonucleotide probe was shown by Northern blotting to hybridize specifically to an approximately 3 kb RNA species from thyroid tissue of patients with Graves' disease, but not to RNA preparations from human or bovine retinal tissue, providing compelling evidence for the specificity of the probe for TPO mRNA. Addition of TSH (10 U/ml) to primary thyroid cultures for 4h led to increased TPO mRNA levels which were maximal after 48 h and significantly higher than basal even after 7 days of co-culture. Activation of TPO mRNA by TSH showed dose dependency over a wide range (0.01-100 mU/ml), with a maximal effect at 10 mU TSH/ml in cells cultured for a period of 72 h. Comparison of TPO mRNA levels with the accumulation of thyroglobulin mRNA levels following stimulation by TSH indicated that the induction of the gene encoding thyroglobulin precedes transcription of the TPO gene. The adenylate cyclase activator forskolin (1-100 μM) mimicked TSH in increasing TPO mRNA levels whilst, in contrast, the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA; 0.01-1 μM) led to levels of TPO mRNA that were lower than basal. Thus TSH induces a specific dose-dependent activation of TPO mRNA which is mimicked by agents which increase cyclic AMP. In contrast, TPA-induced activation of protein kinase C inhibits this response.en_US
dc.languageengen_US
dc.publisherSociety for Endocrinology. The Journal's web site is located at http://jme.endocrinology-journals.org/en_US
dc.relation.ispartofJournal of Molecular Endocrinologyen_US
dc.subject.meshBlotting, Northernen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshForskolin - Pharmacologyen_US
dc.subject.meshGene Expression Regulation - Drug Effectsen_US
dc.subject.meshGraves Disease - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoblottingen_US
dc.subject.meshIodide Peroxidase - Geneticsen_US
dc.subject.meshOligonucleotide Probesen_US
dc.subject.meshRna, Messenger - Biosynthesis - Geneticsen_US
dc.subject.meshTetradecanoylphorbol Acetate - Pharmacologyen_US
dc.subject.meshThyroglobulin - Geneticsen_US
dc.subject.meshThyroid Gland - Cytology - Enzymologyen_US
dc.subject.meshThyrotropin - Pharmacologyen_US
dc.subject.meshTranscription, Genetic - Drug Effectsen_US
dc.titleActivation of the thyroid peroxidase gene in human thyroid cells: Effect of thyrotrophin, forskolin and phorbol esteren_US
dc.typeArticleen_US
dc.identifier.emailKung, AWC:awckung@hku.hken_US
dc.identifier.authorityKung, AWC=rp00368en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1677/jme.0.0030001-
dc.identifier.pmid2742742-
dc.identifier.scopuseid_2-s2.0-0024399645en_US
dc.identifier.volume3en_US
dc.identifier.issue1en_US
dc.identifier.spage1en_US
dc.identifier.epage5en_US
dc.identifier.isiWOS:A1989AE40000001-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridCollison, KS=36902959400en_US
dc.identifier.scopusauthoridBanga, JP=7102475139en_US
dc.identifier.scopusauthoridBarnett, PS=7103395929en_US
dc.identifier.scopusauthoridKung, AWC=7102322339en_US
dc.identifier.scopusauthoridMcGregor, AM=7102812103en_US

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