Spironolactone의 지방조직 기간세포 분화와 11β-hydroxysteroid Dehydrogenase 발현 억제 작용 : Inhibitory Effect of Spironolactone on Differentiation and 11β-HSD Expression in Primarily Cultured Rat Adipocytes
기간세포 Spironolactone 지방조직;
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BACKGROUND : Glucocorticoids have been implicated as pathophysiological mediators of obesity and insulin resistance. Inactive cortisone(E) is converted into active cortisol(F) by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Adipose tissue expresses only 11β-HSD1, and its activity has been implicated to contribute the development of obesity. PURPOSE : We studied the effect of spironolactone on 11β-HSD1 activity and adipocyte differentiation in primary culture of rat adipose stromal- cell(ASC)s. METHODS : ASCs were retrieved from perirenal fat tissue from male SD rats and were activated in culture medium added with isobutylmethylxanthine (M) and insulin(I), to differentiate in the presence or in the absence of cortsone. 11β-HSD1 expression was visualized by immunocytochemistry, and adipocyte differentiation was estimated by triglyceride level. RESULTS ;Adipocyte differentiation was significantly enhanced by E (5×10^(-7) M). The E dependent adipocyte differentiation was dramatically inhibited by pretreatment with spironolactone(S), a minerlocorticoid receptor(MR) antagonist (p = 0.03). On the other hand, S inhibited 11β-HSD1 expression in ASCs. CONCLUSION : These results suggest that spironolactone may inhibit the cortisone dependent differentiation of adipose stromal vascular cells by inhibiting expression of 11β-HSD1.