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17Beta-estradiol inhibits 11beta-hydroxysteroid dehydrogenase type 1 activity in rodent adipocytes.
J Endocrinol. 2009 Jul; 202(1):131-9.JE

Abstract

17Beta-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 11beta-hydroxysteroid dehydrogenase type 1 (11beta-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 E(2) inhibited 11beta-HSD1 activity. Estrogen receptor (ER) antagonists, ICI-182 780 and tamoxifen, failed to reverse this inhibition. A significant inhibitory effect of E(2) on 11beta-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 11beta-HSD1. These results indicate that the inhibition of 11beta-HSD1 by E(2) 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 11beta-HSD1, was unaffected by E(2). A kinetic study revealed that E(2) acted as a non-competitive inhibitor of 11beta-HSD1. The inhibitory effect of E(2) on 11beta-HSD1 was reproduced in adipocytes isolated from rat mesenteric fat depots. This is the first demonstration that E(2) inhibits 11beta-HSD1, thereby providing a novel insight into the anti-obesity mechanism of estrogen.

Authors+Show Affiliations

Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19380458

Citation

Tagawa, Noriko, et al. "17Beta-estradiol Inhibits 11beta-hydroxysteroid Dehydrogenase Type 1 Activity in Rodent Adipocytes." The Journal of Endocrinology, vol. 202, no. 1, 2009, pp. 131-9.
Tagawa N, Yuda R, Kubota S, et al. 17Beta-estradiol inhibits 11beta-hydroxysteroid dehydrogenase type 1 activity in rodent adipocytes. J Endocrinol. 2009;202(1):131-9.
Tagawa, N., Yuda, R., Kubota, S., Wakabayashi, M., Yamaguchi, Y., Kiyonaga, D., Mori, N., Minamitani, E., Masuzaki, H., & Kobayashi, Y. (2009). 17Beta-estradiol inhibits 11beta-hydroxysteroid dehydrogenase type 1 activity in rodent adipocytes. The Journal of Endocrinology, 202(1), 131-9. https://doi.org/10.1677/JOE-09-0021
Tagawa N, et al. 17Beta-estradiol Inhibits 11beta-hydroxysteroid Dehydrogenase Type 1 Activity in Rodent Adipocytes. J Endocrinol. 2009;202(1):131-9. PubMed PMID: 19380458.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 17Beta-estradiol inhibits 11beta-hydroxysteroid dehydrogenase type 1 activity in rodent adipocytes. AU - Tagawa,Noriko, AU - Yuda,Ryosuke, AU - Kubota,Sayaka, AU - Wakabayashi,Midori, AU - Yamaguchi,Yuko, AU - Kiyonaga,Daisuke, AU - Mori,Natsuko, AU - Minamitani,Erika, AU - Masuzaki,Hiroaki, AU - Kobayashi,Yoshiharu, Y1 - 2009/04/20/ PY - 2009/4/22/entrez PY - 2009/4/22/pubmed PY - 2009/7/23/medline SP - 131 EP - 9 JF - The Journal of endocrinology JO - J Endocrinol VL - 202 IS - 1 N2 - 17Beta-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 11beta-hydroxysteroid dehydrogenase type 1 (11beta-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 E(2) inhibited 11beta-HSD1 activity. Estrogen receptor (ER) antagonists, ICI-182 780 and tamoxifen, failed to reverse this inhibition. A significant inhibitory effect of E(2) on 11beta-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 11beta-HSD1. These results indicate that the inhibition of 11beta-HSD1 by E(2) 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 11beta-HSD1, was unaffected by E(2). A kinetic study revealed that E(2) acted as a non-competitive inhibitor of 11beta-HSD1. The inhibitory effect of E(2) on 11beta-HSD1 was reproduced in adipocytes isolated from rat mesenteric fat depots. This is the first demonstration that E(2) inhibits 11beta-HSD1, thereby providing a novel insight into the anti-obesity mechanism of estrogen. SN - 1479-6805 UR - https://www.unboundmedicine.com/medline/citation/19380458/17Beta_estradiol_inhibits_11beta_hydroxysteroid_dehydrogenase_type_1_activity_in_rodent_adipocytes_ L2 - https://joe.bioscientifica.com/doi/10.1677/JOE-09-0021 DB - PRIME DP - Unbound Medicine ER -