17β-Estradiol inhibits 11β-hydroxysteroid dehydrogenase type 1 activity in rodent adipocytes

被引:21
|
作者
Tagawa, Noriko [1 ]
Yuda, Ryosuke [1 ]
Kubota, Sayaka [1 ]
Wakabayashi, Midori [1 ]
Yamaguchi, Yuko [1 ]
Kiyonaga, Daisuke [1 ]
Mori, Natsuko [1 ]
Minamitani, Erika [1 ]
Masuzaki, Hiroaki [2 ]
Kobayashi, Yoshiharu [1 ]
机构
[1] Kobe Pharmaceut Univ, Dept Med Biochem, Higashinada Ku, Kobe, Hyogo 6588558, Japan
[2] Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Sakyo Ku, Kyoto 6068507, Japan
关键词
HEPATIC INSULIN SENSITIVITY; ADIPOSE-TISSUE; HEXOSE-6-PHOSPHATE DEHYDROGENASE; ESTROGEN-RECEPTOR; GLUCOSE-DEHYDROGENASE; METABOLIC SYNDROME; RAT ADIPOCYTES; STROMAL CELLS; FUNCTIONAL-RELATIONSHIP; SELECTIVE-INHIBITION;
D O I
10.1677/JOE-09-0021
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
17 beta-Estradiol (E-2) serves as an anti-obesity steroid; however, the mechanism underlying this effect has not been fully clarified. The effect of E-2 on adipocytes opposes that of glucocorticoids, which potentiate adipogenesis and anabolic lipid metabolism. The key to the intracellular activation Of glucocorticoid in adipocytes is 11 beta-hydroxy-steroid dehydrogenase type 1 (11 beta-HSD1), which catalyses the production of active glucocorticoids (cortisol in humans and corticosterone in rodents) from inactive 11-keto steroids (cortisone in humans and 11-dehydro-corticosterone in rodents), Using differentiated 3T3-L1 adipocytes, we showed that E-2 inhibited 11 beta-HSD1 activity. Estrogen receptor (ER) antagonists, ICI-182 780 and tamoxifen, failed to reverse this inhibition. A significant inhibitory effect of E-2 on 11 beta-HSD1 activity was observed within 5-10 min. Furthermore, acetylation or alpha-epimerization of 17-hydroxy group of E-2 attenuated the inhibitory effect on 11 beta-HSD1. These results indicate that the inhibition of 11 beta-HSD1 by E-2 depends oil neither all ER-dependent route, transcriptional pathway nor nonspecific fashion. Hexose-6-phosphate dehydrogenase, which provides the cofactor NADPH for full activation of 11 beta-HSD1, was unaffected by E-2. A kinetic study revealed that E-2 acted as a non-competitive inhibitor of 11 beta-HSD1. The inhibitory effect of E-2 on 11 beta-HSD1 was reproduced in adipocytes isolated front rat mesenteric fat depots. This is the first demonstration that E-2 inhibits 11 beta-HSD1, thereby providing a novel insight into the anti-obesity mechanism of estrogen. Journal of Endocrinology (2009) 202, 131-139
引用
收藏
页码:131 / 139
页数:9
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