ECE2007 Oral Communications Neuroendocriology basis (7 abstracts)
Metabolic abnormalities in patients with adrenal adenomas may be associated with BclI polymorphism in the glucocorticoid receptor (GR) gene and expression of tumor-specific hsp70 isoforms
Svetozar Damjanovic , Jadranka Antic , Bojana Beleslin , Sanja Ognjanovic , Jovana Vignjevic , Milan Petakov , Djuro Macut , Ivan Paunovic , Tatjana Isailovic , Bojana Popovic & Ivana Bozic
Institute for Endocrinology, Diabetes and Metabolic Diseases, Belgrade, Serbia.
Introduction: Intronic BclI polymorphism of glucocorticoid receptor (GR) gene and adrenal adenomas of incidental discovery are frequently associated with metabolic syndrome. We studied in these patients metabolic and hormonal parameters, the sequence alteration in BclI polymorphism of the GR gene from constitutive DNA and the expression of Hsp70 within the tumor and in tissue adjacently to tumor.
Patients and methods: We assessed 114 healthy subjects (79 men; age range 21–68 years) and 30 patients operated due to non-functioning adrenal mass (5 men; age range 36–76 years). Besides clininical and anthropometrical assessment, morning cortisol and fasting insulin levels were determined. DNA was obtained from leucocytes and after amplification, PCR fragments were digested with BclI enzyme. Subsequently, the sequence of the fragments was analyzed. Equal amounts of protein obtained from total cell lysates of adenomatous and adjacent normal adrenal tissue was resolved by 9% SDS-PAGE and transferred to nitrocellulose membranes (Western blot analysis).
Results: We found a G-to-C transition in the second intron of GR gene in 24 of 26 (92%) patients that is significantly higher frequency of the larger allele within patients than in normal population (42% vs 4.2%; P<0.001). Patients and controls had similar BMI and morning cortisol levels. However, the frequency of diabetes type 2, and hypertension were significantly higher in patients with adrenal tumor (P=0.002 for both) and these patients had significantly higher HOMA index than controls (6.8±1.9 vs 2.9±0.1; P<0.001). In all tumor tissues two isoforms of Hsp70 co-expressed while only higher molecular weight isoform was detected in adjacent normal tissue.
Conclusion: Increased sensitivity to glucocorticoids associated with specific BclI polymorphism of GR gene and altered trafficking of GR by the Hsp90/Hsp70-based chaperone machinery within adrenal adenoma seems to play role in the development of insulin resistance in these patients.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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