HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) All Versions of this Article: JOE-09-0021v1 202/1/131    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tagawa, N. Articles by Kobayashi, Y. Search for Related Content PubMed PubMed Citation Articles by Tagawa, N. Articles by Kobayashi, Y.

N Tagawa, Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan
R Yuda, Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan
S Kubota, Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan
M Wakabayashi, Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan
Y Yamaguchi, Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan
D Kiyonaga, Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan
N Mori, Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan
E Minamitani, Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan
H Masuzaki, Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
Y Kobayashi, Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, 658-8558, Japan

Correspondence: Yoshiharu Kobayashi, Email: yoshi{at}kobepharma-u.ac.jp

17β-Estradiol serves as an anti-obesity steroid; however, the mechanism underlying this effect has not been fully clarified. The effect of 17β-estradiol on adipocytes opposes that of glucocorticoids, which potentiate adipogenesis and anabolic lipid metabolism. The key to the intracellular activation of glucocorticoid in adipocytes is 11β-hydroxysteroid dehydrogenase type 1 (11β-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-dehydrocorticosterone in rodents). Using differentiated 3T3-L1 adipocytes, we showed that 17β-estradiol inhibited 11β-HSD1 activity. Estrogen receptor (ER) antagonists, ICI182,780 and tamoxifen, failed to reverse this inhibition. Significant inhibitory effect of 17β-estradiol on 11β-HSD1 activity was observed within 5-10 min. Further, acetylation or -epimerization of 17-hydroxy group of 17β-estradiol attenuated the inhibitory effect on 11β-HSD1. These results indicate that the inhibition of 11β-HSD1 by 17β-estradiol depends on neither an ER-dependent route, transcriptional pathway nor non-specific fashion. Hexose-6-phosphate dehydrogenase, which provides the cofactor NADPH for full activation of 11β-HSD1, was unaffected by 17β-estradiol. A kinetic study revealed that 17β-estradiol acted as a non-competitive inhibitor of 11β-HSD1. The inhibitory effect of 17β-estradiol on 11β-HSD1 was reproduced in adipocytes isolated from rat mesenteric fat depots. This is the first demonstration that 17β-estradiol inhibits 11β-HSD1, thereby providing a novel insight into the anti-obesity mechanism of estrogen.