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Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity

 Ann W Kinyua  ;  Khanh V Doan  ;  Dong Joo Yang  ;  My Khanh Q Huynh  ;  Yun-Hee Choi  ;  Dong Min Shin  ;  Ki Woo Kim 
 SCIENTIFIC REPORTS, Vol.8(1) : 5025, 2018 
Journal Title
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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.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ki Woo(김기우) ORCID logo https://orcid.org/0000-0002-7790-1515
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
Choi, Yun Hee(최윤희) ORCID logo https://orcid.org/0000-0002-3519-8841
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