The orphan nuclear receptor SF-1 (steroidogenic factor 1) is highly expressed in the pituitary, gonad and adrenal glands and plays key roles at all levels of the hypothalamic–pituitary–steroidogenic tissue axis. In the present study, we show that PGC-1α [PPARγ (peroxisome-proliferator-activated receptor γ) co-activator 1α] interacts with and co-activates SF-1 to induce LHβ (luteinizing hormone β) and αGSU (α-glycoprotein subunit) gene expression, subsequently leading to the increased secretion of LH in pituitary gonadotrope-derived αT3-1 cells. PGC-1α co-activation of LHβ expression requires an SF-1-binding element [GSE (gonadotrope-specific element)] mapped to the promoter region of LHβ. Mammalian two-hybrid and co-immunoprecipitation assays, as well as GST (glutathione transferase) pull-down experiments demonstrated that PGC-1α interacts with SF-1 in vivo and in vitro. Additionally, PGC-1α stimulates the expression of Cyp11b2 (aldosterone synthase gene), Cyp11b1 (steroid 11β-hydroxylase gene) and P450scc (cholesterol side-chain cleavage enzyme), and the synthesis of aldosterone in adrenal-cortex-derived Y-1 cells. Chromatin immunoprecipitation assays confirmed that endogenous PGC-1α co-localizes with SF-1 in the LHβ and Cyp11b2 promoter region. Knockdown of endogenous SF-1 by siRNA (small interfering RNA) abolished the PGC-1α induction of LHβ and Cyp11b2 gene expression in αT3-1 and Y-1 cells respectively. Finally, we demonstrated that PGC-1α induces SF-1 gene expression in both αT3-1 and Y-1 cells. Taken together, our findings reveal the potential role of PGC-1α and suggest that it may play important roles in steroidogenesis, gonad development and sex differentiation through SF-1.
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Research Article|
November 25 2010
PPARγ co-activator-1α co-activates steroidogenic factor 1 to stimulate the synthesis of luteinizing hormone and aldosterone
Liuluan Zhu;
Liuluan Zhu
1
*National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
†Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
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Yaojun Ke;
Yaojun Ke
1
‡Department of Interventional Radiology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430064, China
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Di Shao;
Di Shao
*National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
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Ying Cui;
Ying Cui
*National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
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Aijun Qiao;
Aijun Qiao
*National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
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Xiaojun Liu;
Xiaojun Liu
*National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
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Fude Fang;
Fude Fang
2
*National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
2Correspondence may be addressed to either of these authors (email fangfd@vip.sina.com or changy@ibms.pumc.edu.cn).
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Yongsheng Chang
Yongsheng Chang
2
*National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
2Correspondence may be addressed to either of these authors (email fangfd@vip.sina.com or changy@ibms.pumc.edu.cn).
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Publisher: Portland Press Ltd
Received:
March 30 2010
Revision Received:
September 27 2010
Accepted:
October 05 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 432 (3): 473–486.
Article history
Received:
March 30 2010
Revision Received:
September 27 2010
Accepted:
October 05 2010
Citation
Liuluan Zhu, Yaojun Ke, Di Shao, Ying Cui, Aijun Qiao, Xiaojun Liu, Fude Fang, Yongsheng Chang; PPARγ co-activator-1α co-activates steroidogenic factor 1 to stimulate the synthesis of luteinizing hormone and aldosterone. Biochem J 15 December 2010; 432 (3): 473–486. doi: https://doi.org/10.1042/BJ20100460
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