TY  - JOUR
AU  - Damjanović, Svetozar S
AU  - Antić, Jadranka A
AU  - Ilić, Bojana B
AU  - Beleslin-Cokić, Bojana B
AU  - Ivović, Miomira S
AU  - Ognjanović, Sanja I
AU  - Isailović, Tatjana V
AU  - Popović, Bojana M
AU  - Bozić, Ivana B
AU  - Tatić, Svetislav B
AU  - Matić, Gordana
AU  - Todorović, Vera N
AU  - Paunović, Ivan R
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1085
AB  - 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
T2  - Molecular Medicine
T1  - Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids
IS  - 11
VL  - 18
SP  - 189
EP  - 1465
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1085
ER  - 

@article{
author = "Damjanović, Svetozar S and Antić, Jadranka A and Ilić, Bojana B and Beleslin-Cokić, Bojana B and Ivović, Miomira S and Ognjanović, Sanja I and Isailović, Tatjana V and Popović, Bojana M and Bozić, Ivana B and Tatić, Svetislav B and Matić, Gordana and Todorović, Vera N and Paunović, Ivan R",
year = "2012",
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",
journal = "Molecular Medicine",
title = "Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids",
number = "11",
volume = "18",
pages = "189-1465",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1085"
}

Damjanović, S. S., Antić, J. A., Ilić, B. B., Beleslin-Cokić, B. B., Ivović, M. S., Ognjanović, S. I., Isailović, T. V., Popović, B. M., Bozić, I. B., Tatić, S. B., Matić, G., Todorović, V. N.,& Paunović, I. R.. (2012). Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids. in Molecular Medicine, 18(11), 189-1465.
https://hdl.handle.net/21.15107/rcub_ibiss_1085

Damjanović SS, Antić JA, Ilić BB, Beleslin-Cokić BB, Ivović MS, Ognjanović SI, Isailović TV, Popović BM, Bozić IB, Tatić SB, Matić G, Todorović VN, Paunović IR. Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids. in Molecular Medicine. 2012;18(11):189-1465.
https://hdl.handle.net/21.15107/rcub_ibiss_1085 .

Damjanović, Svetozar S, Antić, Jadranka A, Ilić, Bojana B, Beleslin-Cokić, Bojana B, Ivović, Miomira S, Ognjanović, Sanja I, Isailović, Tatjana V, Popović, Bojana M, Bozić, Ivana B, Tatić, Svetislav B, Matić, Gordana, Todorović, Vera N, Paunović, Ivan R, "Glucocorticoid Receptor and Molecular Chaperones in the Pathogenesis of Adrenal Incidentalomas: Potential Role of Reduced Sensitivity to Glucocorticoids" in Molecular Medicine, 18, no. 11 (2012):189-1465,
https://hdl.handle.net/21.15107/rcub_ibiss_1085 .