Abstract

Development of metabolic syndrome is associated with hyperactivity of the HPA axis characterized by elevated levels of circulating adrenal hormones including cortisol and aldosterone. However, the molecular mechanism leading to the dysregulation of the HPA axis is not well elucidated. In this study, we found that insulin regulates adrenal steroidogenesis by increasing the expression and activity of steroidogenic factor 1 (SF-1) both in vitro and in vivo and this insulin effect was partly through inhibition of FoxO1. Specifically, insulin increased the protein and RNA levels of SF-1 and steroidogenic target genes. Further, adrenal SF-1 expression was significantly increased by hyperactivation of insulin signaling in mice. Together with the elevated SF-1 expression in adrenal glands, hyperactivation of insulin signaling led to increased aldosterone and corticosterone levels. On the other hand, suppressing the insulin signaling using streptozotocin markedly reduced the expression of adrenal SF-1 in mice. In addition, overexpression of FoxO1 significantly suppressed SF-1 and its steroidogenic target genes implying that the positive effect of insulin on SF-1 activity might be through suppression of FoxO1 in the adrenal gland. Taken together, these results indicate that insulin regulates adrenal steroidogenesis through coordinated control of SF-1 and FoxO1.

Details

Title
Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity
Author
Kinyua, Ann W 1 ; Doan, Khanh V 2 ; Yang, Dong Joo 3 ; My Khanh Q Huynh 1 ; Choi, Yun-Hee 4 ; Shin, Dong Min 5 ; Ki Woo Kim 3   VIAFID ORCID Logo 

 Departments of Pharmacology and Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, Korea 
 Departments of Pharmacology and Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, Korea; Department of Pharmacology, Tan Tao University, School of Medicine, Tan Tao University Avenue Tan Duc E., City, Duc Hoa, Long An, Vietnam 
 Departments of Pharmacology and Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, Korea; Department of Oral Biology, BK21 PLUS, Yonsei University College of Dentistry, Seoul, Korea 
 Anti-aging Research Institute of BIO-FD&C Co. Ltd., Incheon, Korea 
 Department of Oral Biology, BK21 PLUS, Yonsei University College of Dentistry, Seoul, Korea 
Pages
1-9
Publication year
2018
Publication date
Mar 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2017036358
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.