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 .

TY  - JOUR
AU  - Vojnović-Milutinović, Danijela
AU  - Macut, Đuro P
AU  - Bozić, Ivana B
AU  - Brkljačić, Jelena
AU  - Damjanović, Svetozar S
AU  - Matić, Gordana
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1248
AB  - Introduction: Molecular mechanisms underlying pathophysiology of polycystic ovary syndrome (PCOS), especially those related to cortisol signaling, are poorly understood. We hypothesized that modulation of glucocorticoid receptor (GR) expression and function, may underlie possible PCOS-related impairment of feedback inhibition of hypothalamic-pituitary-adrenocortical (HPA) axis activity and thus contribute to increased adrenal androgen production in women with PCOS. Materials and Methods: 24 normal-weight and 31 obese women with PCOS were compared to 25 normal-weight controls. Fasting blood samples were collected for measurements of serum concentrations of dehydroepiandrosterone sulfate, testosterone, sex hormone-binding globulin, insulin, basal cortisol and cortisol after oral administration of 0.5 mg dexamethasone. Concentrations of GR mRNA, GR protein, mineralocorticoid receptor (MR) protein and heat shock proteins (Hsps), as well as the number of GR per cell (B(max)) and its equilibrium dissociation constant (K(D)) were measured in isolated peripheral blood mononuclear cells. Results: An increase in HPA axis sensitivity to dexamethasone, an elevation of the GR protein concentration, and unaltered receptor functional status were found in both normal-weight and obese women with PCOS vs. healthy controls. Lymphocyte MR, Hsp90 and Hsp70 concentrations, and MR/GR ratio were similar in all groups. Correlation between B(max) and K(D) was weaker in the group of obese women with PCOS than in the other 2 groups. Conclusions: The results did not confirm the initial hypothesis, but imply that PCOS is associated with increased GR protein concentration and HPA axis sensitivity to dexamethasone.
T2  - Experimental and Clinical Endocrinology & Diabetes
T1  - Hypothalamic-Pituitary-Adrenocortical Axis Hypersensitivity and Glucocorticoid Receptor Expression and Function in Women with Polycystic Ovary Syndrome
IS  - 10
VL  - 119
EP  - 643
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1248
ER  - 

@article{
author = "Vojnović-Milutinović, Danijela and Macut, Đuro P and Bozić, Ivana B and Brkljačić, Jelena and Damjanović, Svetozar S and Matić, Gordana",
year = "2011",
abstract = "Introduction: Molecular mechanisms underlying pathophysiology of polycystic ovary syndrome (PCOS), especially those related to cortisol signaling, are poorly understood. We hypothesized that modulation of glucocorticoid receptor (GR) expression and function, may underlie possible PCOS-related impairment of feedback inhibition of hypothalamic-pituitary-adrenocortical (HPA) axis activity and thus contribute to increased adrenal androgen production in women with PCOS. Materials and Methods: 24 normal-weight and 31 obese women with PCOS were compared to 25 normal-weight controls. Fasting blood samples were collected for measurements of serum concentrations of dehydroepiandrosterone sulfate, testosterone, sex hormone-binding globulin, insulin, basal cortisol and cortisol after oral administration of 0.5 mg dexamethasone. Concentrations of GR mRNA, GR protein, mineralocorticoid receptor (MR) protein and heat shock proteins (Hsps), as well as the number of GR per cell (B(max)) and its equilibrium dissociation constant (K(D)) were measured in isolated peripheral blood mononuclear cells. Results: An increase in HPA axis sensitivity to dexamethasone, an elevation of the GR protein concentration, and unaltered receptor functional status were found in both normal-weight and obese women with PCOS vs. healthy controls. Lymphocyte MR, Hsp90 and Hsp70 concentrations, and MR/GR ratio were similar in all groups. Correlation between B(max) and K(D) was weaker in the group of obese women with PCOS than in the other 2 groups. Conclusions: The results did not confirm the initial hypothesis, but imply that PCOS is associated with increased GR protein concentration and HPA axis sensitivity to dexamethasone.",
journal = "Experimental and Clinical Endocrinology & Diabetes",
title = "Hypothalamic-Pituitary-Adrenocortical Axis Hypersensitivity and Glucocorticoid Receptor Expression and Function in Women with Polycystic Ovary Syndrome",
number = "10",
volume = "119",
pages = "643",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1248"
}

Vojnović-Milutinović, D., Macut, Đ. P., Bozić, I. B., Brkljačić, J., Damjanović, S. S.,& Matić, G.. (2011). Hypothalamic-Pituitary-Adrenocortical Axis Hypersensitivity and Glucocorticoid Receptor Expression and Function in Women with Polycystic Ovary Syndrome. in Experimental and Clinical Endocrinology & Diabetes, 119(10).
https://hdl.handle.net/21.15107/rcub_ibiss_1248

Vojnović-Milutinović D, Macut ĐP, Bozić IB, Brkljačić J, Damjanović SS, Matić G. Hypothalamic-Pituitary-Adrenocortical Axis Hypersensitivity and Glucocorticoid Receptor Expression and Function in Women with Polycystic Ovary Syndrome. in Experimental and Clinical Endocrinology & Diabetes. 2011;119(10):null-643.
https://hdl.handle.net/21.15107/rcub_ibiss_1248 .

Vojnović-Milutinović, Danijela, Macut, Đuro P, Bozić, Ivana B, Brkljačić, Jelena, Damjanović, Svetozar S, Matić, Gordana, "Hypothalamic-Pituitary-Adrenocortical Axis Hypersensitivity and Glucocorticoid Receptor Expression and Function in Women with Polycystic Ovary Syndrome" in Experimental and Clinical Endocrinology & Diabetes, 119, no. 10 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1248 .

TY  - JOUR
AU  - Macut, Đuro P
AU  - Vojnović-Milutinović, Danijela
AU  - Bozić, Ivana B
AU  - Matić, Gordana
AU  - Brkljačić, Jelena
AU  - Panidis, Dimitrios
AU  - Petakov, Milan S
AU  - Spanos, Nikolaos
AU  - Bjekić, Jelica
AU  - Stanojlović, Olivera P
AU  - Petrović-Milinković, Anđela
AU  - Radojicić, Zoran A
AU  - Damjanović, Svetozar S
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1402
AB  - Glucocorticoid receptor (GR) transduces the glucocorticoid (GC) signal that could lead to metabolic derangements depending on the tissue responsiveness to GC. We aimed to investigate possible causative relation of the GR functional properties in peripheral blood mononuclear cells of women with polycystic ovary syndrome (PCOS), with their clinical and biochemical characteristics. Thirty women with PCOS [mean age: 26.5 +/- A 5.1 years, mean body mass index (BMI) 24.5 +/- A 5 kg/m(2)], and thirty respective controls were analyzed for the number of GR sites per cell (B (max)), apparent equilibrium dissociation constant (K (d)), and binding potency (GR potency). A strong association between B (max) and K (d) (r = 0.70, P < 0.0001), and GR potency with age (r = 0.49, P = 0.009) was observed in PCOS women. The multiple regression analyses within the PCOS group revealed that independent predictors for K (d) were BMI, total cholesterol, and dehydroepiandrosterone-sulfate (DHEA-S) (r = 0.58, P = 0.038), while for GR potency (r = 0.687, P = 0.013) were age, BMI, DHEA-S, and basal cortisol concentration. The results suggest that PCOS pathophysiology may be related to alterations of a cross stalk between glucocorticoid signaling, age, and metabolic parameters. These findings should be further explored in studies on the role of GR in PCOS-related metabolic derangements.
T2  - Endocrine
T1  - Age, body mass index, and serum level of DHEA-S can predict glucocorticoid receptor function in women with polycystic ovary syndrome
IS  - 1
VL  - 37
EP  - 134
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1402
ER  - 

@article{
author = "Macut, Đuro P and Vojnović-Milutinović, Danijela and Bozić, Ivana B and Matić, Gordana and Brkljačić, Jelena and Panidis, Dimitrios and Petakov, Milan S and Spanos, Nikolaos and Bjekić, Jelica and Stanojlović, Olivera P and Petrović-Milinković, Anđela and Radojicić, Zoran A and Damjanović, Svetozar S",
year = "2010",
abstract = "Glucocorticoid receptor (GR) transduces the glucocorticoid (GC) signal that could lead to metabolic derangements depending on the tissue responsiveness to GC. We aimed to investigate possible causative relation of the GR functional properties in peripheral blood mononuclear cells of women with polycystic ovary syndrome (PCOS), with their clinical and biochemical characteristics. Thirty women with PCOS [mean age: 26.5 +/- A 5.1 years, mean body mass index (BMI) 24.5 +/- A 5 kg/m(2)], and thirty respective controls were analyzed for the number of GR sites per cell (B (max)), apparent equilibrium dissociation constant (K (d)), and binding potency (GR potency). A strong association between B (max) and K (d) (r = 0.70, P < 0.0001), and GR potency with age (r = 0.49, P = 0.009) was observed in PCOS women. The multiple regression analyses within the PCOS group revealed that independent predictors for K (d) were BMI, total cholesterol, and dehydroepiandrosterone-sulfate (DHEA-S) (r = 0.58, P = 0.038), while for GR potency (r = 0.687, P = 0.013) were age, BMI, DHEA-S, and basal cortisol concentration. The results suggest that PCOS pathophysiology may be related to alterations of a cross stalk between glucocorticoid signaling, age, and metabolic parameters. These findings should be further explored in studies on the role of GR in PCOS-related metabolic derangements.",
journal = "Endocrine",
title = "Age, body mass index, and serum level of DHEA-S can predict glucocorticoid receptor function in women with polycystic ovary syndrome",
number = "1",
volume = "37",
pages = "134",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1402"
}

Macut, Đ. P., Vojnović-Milutinović, D., Bozić, I. B., Matić, G., Brkljačić, J., Panidis, D., Petakov, M. S., Spanos, N., Bjekić, J., Stanojlović, O. P., Petrović-Milinković, A., Radojicić, Z. A.,& Damjanović, S. S.. (2010). Age, body mass index, and serum level of DHEA-S can predict glucocorticoid receptor function in women with polycystic ovary syndrome. in Endocrine, 37(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1402

Macut ĐP, Vojnović-Milutinović D, Bozić IB, Matić G, Brkljačić J, Panidis D, Petakov MS, Spanos N, Bjekić J, Stanojlović OP, Petrović-Milinković A, Radojicić ZA, Damjanović SS. Age, body mass index, and serum level of DHEA-S can predict glucocorticoid receptor function in women with polycystic ovary syndrome. in Endocrine. 2010;37(1):null-134.
https://hdl.handle.net/21.15107/rcub_ibiss_1402 .

Macut, Đuro P, Vojnović-Milutinović, Danijela, Bozić, Ivana B, Matić, Gordana, Brkljačić, Jelena, Panidis, Dimitrios, Petakov, Milan S, Spanos, Nikolaos, Bjekić, Jelica, Stanojlović, Olivera P, Petrović-Milinković, Anđela, Radojicić, Zoran A, Damjanović, Svetozar S, "Age, body mass index, and serum level of DHEA-S can predict glucocorticoid receptor function in women with polycystic ovary syndrome" in Endocrine, 37, no. 1 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1402 .