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Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids
dc.creator | Damjanović, Svetozar S | |
dc.creator | Antić, Jadranka A | |
dc.creator | Ilić, Bojana B | |
dc.creator | Beleslin-Cokić, Bojana B | |
dc.creator | Ivović, Miomira S | |
dc.creator | Ognjanović, Sanja I | |
dc.creator | Isailović, Tatjana V | |
dc.creator | Popović, Bojana M | |
dc.creator | Bozić, Ivana B | |
dc.creator | Tatić, Svetislav B | |
dc.creator | Matić, Gordana | |
dc.creator | Todorović, Vera N | |
dc.creator | Paunović, Ivan R | |
dc.date.accessioned | 2017-11-23T11:12:09Z | |
dc.date.available | 2015-11-17T10:26:51Z | |
dc.date.issued | 2012 | sr |
dc.identifier.issn | 1076-1551 | sr |
dc.identifier.other | Rad_konverzija_3080 | sr |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/1085 | |
dc.description.abstract | Glucocorticoid (GC) sensitivity depends on glucocorticoid receptor (GR) and heat shock proteins (Hsps). We investigated whether common GR genes (ER22/23EK N363S, BclI, and 9 beta) and adrenocorticotropin receptor promoter polymorphisms influence susceptibility for unilateral adrenal incidentaloma (AI), plus GR and Hsp expression in tumorous (n = 19), peritumorous (n = 13) and normal adrenocortical (n = 11) tissues. Patients (n = 112), population-matched controls (n = 100) and tumor tissues (n = 32) were genotyped for these polymorphisms. Postdexamethasone serum cortisol was higher in patients (p<0.001). GR gene variants, larger allele of BclI (odds ratio (OR) 2.9; 95% confidence interval (CI) 1.7-5.1; p < 0.001) and minor allele of 9 beta (OR 3.0; 95% CI 1.6-5.7; p < 0.001) were independent predictors of Al. In patients, the first allele is linked with larger tumors (p = 0.002) and the latter with higher postdexamethasone cortisol levels (p = 0.025). Both allele carriers had lesser waist circumference (p = 0.02), similar adrenocorticotropin and higher basal (p = 0.024) and postdexamethasone cortisol concentrations (p < 0.001). Tumorous and constitutional genotypes were similar. GR-D is the major receptor isoform in normal adrenal cortex by Western blotting. Loss of other receptor isoforms, decrease in immunostaining for GR (p < 0.0001), underexpression of chaperones (p <= 0.01) and the presence of inducible Hsp70 were found in adenomas. In conclusion, GR gene variants, C allele of BclI and minor allele of 9 beta, are associated with Als. Their concurrent presence in patients reduces GC sensitivity Normal adrenal cortex preferentially expresses GR-D. In adenomas, the lack of other GR isoforms and underexpression of heat shock proteins perhaps permanently impair GC signaling, which could promote dysregulated cortisol production and tumor growth. The innate GC sensitivity probably modifies these effects. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00261 | en |
dc.description.sponsorship | Ministry of Science and Technological Development of Serbia [III41009] | sr |
dc.language.iso | English | sr |
dc.rights | restrictedAccess | |
dc.source | Molecular Medicine | sr |
dc.title | Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Огњановић, Сања И; Матић, Гордана М.; Тодоровић, Вера Н; Белеслин-Цокић, Бојана Б; Татић, Светислав Б; Ивовић, Миомира С; Поповић, Бојана М; Исаиловић, Татјана В; Дамјановић, Светозар С; Aнтић, Јадранка A; Пауновић, Иван Р; Илић, Бојана Б; Бозић, Ивана Б; | |
dc.citation.issue | 11 | sr |
dc.citation.volume | 18 | sr |
dc.citation.spage | 189 | sr |
dc.citation.epage | 1465 | sr |
dc.type.version | publishedVersion | en |
dc.citation.rank | M21 | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_ibiss_1085 |
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