Cases of Borderline in Vitro Constitutive Thyrotropin Receptor Activity: How to Decide Whether a Thyrotropin Receptor Mutation Is Constitutively Active or Not?

dc.authorid0000-0001-5291-8620
dc.authorid0000-0002-4732-2934
dc.authorscopusid15070736900
dc.authorscopusid16241650400
dc.authorscopusid8416126500
dc.authorscopusid9275130900
dc.authorscopusid57195256086
dc.authorscopusid29067965900
dc.authorscopusid7202378037
dc.authorwosidBircan, Rıfat/A-7344-2018
dc.contributor.authorMueller, Sandra
dc.contributor.authorGözü, Hülya İliksu
dc.contributor.authorBircan, Rifat
dc.contributor.authorJaeschke, Holger
dc.contributor.authorEszlinger, Markus
dc.contributor.authorLueblinghoff, Julia
dc.contributor.authorPaschke, Ralf
dc.date.accessioned2022-05-11T14:28:24Z
dc.date.available2022-05-11T14:28:24Z
dc.date.issued2009
dc.departmentFakülteler, Fen Edebiyat Fakültesi, Biyoloji Bölümü
dc.description.abstractBackground: Previous in vitro data for several constitutively activating thyrotropin receptor (TSHR) mutations reported divergent results for the constitutive activity of the same mutations. Moreover, several case reports have highlighted the difficulties in determining whether a TSHR mutation is constitutively active or not. Retrospectively, this has repeatedly been the case for mutants with only a slight increase of basal cAMP activity. We re-examined 10 previously described TSHR germline mutations with minor increases of basal cAMP activity and analyzed the influences of the cell line and vector system on the basal receptor activity. Methods: TSHR mutations were characterized by determination of cell surface expression, cAMP accumulation, and linear regression analysis of constitutive activity. Results: Re-examination of the previously described constitutively active TSHR germline mutations did not show constitutive activity for R310C and N670S as tested in COS-7 cells and confirmed constitutive activity for the other eight mutations. However, mutant N670S showed a slight but significant increase of basal activity measured by linear regression analysis when analyzed in HEKGT cells transiently transfected with pcDNA but not with the pSVL vector. This was not the case for R310C. Conclusions: Our findings indicate that current methods to precisely classify mutants with only a slight increase of the basal activity as constitutively active are limited. The results concerning the level of the basal activity can be influenced by the vector and/or the cell system. A comprehensive clinical characterization of the respective patients appears as a necessary and promising adjunct for the activity classification of these borderline mutations.
dc.description.sponsorshipDeutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [DFG/Pa 423/14-1]
dc.description.sponsorshipWe thank Eileen Boesenberg and Saskia Fiedler (Department of Internal Medicine III, University of Leipzig, D-04103 Leipzig, Germany) for her excellent technical assistance and Micheline Misrahi (Laboratory of Molecular Genetics, Pharmacology and Hormones, University of Paris, France) and Susanne Neumann (Clinical Endocrinology Branch, NIDDK, National Institutes of Health, Bethesda, MD) for critical reading of the manuscript. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG/Pa 423/14-1).
dc.identifier.doi10.1089/thy.2009.0006
dc.identifier.endpage773
dc.identifier.issn1050-7256
dc.identifier.issn1557-9077
dc.identifier.issue7en_US
dc.identifier.pmid19583488
dc.identifier.scopus2-s2.0-67749131205
dc.identifier.scopusqualityQ1
dc.identifier.startpage765
dc.identifier.urihttps://doi.org/10.1089/thy.2009.0006
dc.identifier.urihttps://hdl.handle.net/20.500.11776/6810
dc.identifier.volume19
dc.identifier.wosWOS:000267762900012
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorBircan, Rifat
dc.language.isoen
dc.publisherMary Ann Liebert, Inc
dc.relation.ispartofThyroid
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAutosomal-Dominant Hyperthyroidism
dc.subjectHyperfunctioning Thyroid Adenomas
dc.subjectStimulating Hormone-Receptor
dc.subjectTsh Receptor
dc.subjectGermline Mutation
dc.subjectSomatic Mutations
dc.subjectNonautoimmune Hyperthyroidism
dc.subjectTransmembrane Domain
dc.subjectExtracellular Domain
dc.subjectCongenital Hyperthyroidism
dc.titleCases of Borderline in Vitro Constitutive Thyrotropin Receptor Activity: How to Decide Whether a Thyrotropin Receptor Mutation Is Constitutively Active or Not?
dc.typeArticle

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