PS-C21-4: EPIGENETIC ALTERATION OF 11B;-HYDROXYSTEROID DEHYDROGENASE 1 IN THE ADIPOSE TISSUE OF PATIENTS WITH ENDOCRINE HYPERTENSION

Abstract

Objective: 11Beta-hydroxysteroid dehydrogenase 1 (11β;-HSD1) is a key enzyme involved in metabolic syndrome. The epigenetic control of 11β;-HSD1 is unclear. We examined the 11β;-HSD1 mRNA level and methylation status of the promoter region of the 11β;-HSD1 gene in the adipose tissue of patients with endocrine hypertension. Methods: We evaluated 8 adipose tissue specimens from patients with subclinical Cushing syndrome (SCS) due to cortisol-producing adenomas, 10 tissue specimens from patients with primary aldosteronism due to aldosterone-producing adenoma (APA) and 7 tissue specimens from patients with non-functioning adrenal adenoma (NFA). SCS and primary aldosteronism were diagnosed according to the guideline of the Japanese Endocrine Society. The mRNA level of 11β;-HSD1 was quantified using a real-time PCR. Isolated DNA was treated with bisulfite and amplified using primers specific for the human 11β;-HSD1 promoter region. Results: The glycohemoglobin level was significantly higher in patients with SCS or APA compared with those with NFA (p < 0.05). Blood pressure was significantly elevated in patients with APA compared with those with SCS or NFA (p < 0.01). The 11β;-HSD1 mRNA level was significantly increased in the adipose tissues of SCS and APA compared with NFA patients (p < 0.05). The methylation ratio was significantly lower in SCS compared with APA or NFA patients (p < 0.05). Conclusion: 11β;-HSD1 gene expression is partly controlled by an epigenetic mechanism in human tissues. The pathophysiological roles of epigenetic control of 11β;-HSD1 gene expression in adipose tissue requires further study.