Research Papers:

Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression

Xueting Wang, Longlu Pan, Zhiran Zou, Dan Wang, Yapeng Lu, Zhangji Dong and Li Zhu _

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Oncotarget. 2017; 8:16401-16413. https://doi.org/10.18632/oncotarget.14842

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Xueting Wang1,*, Longlu Pan2,*, Zhiran Zou1, Dan Wang1, Yapeng Lu1, Zhangji Dong3, Li Zhu1,4

1Department of Biochemistry, Institute for Nautical Medicine, Nantong University, China

2Department of Rehabilitation of the Six People’s Hospital of Nantong, Jiangsu, China

3Co-Innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China

4Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, China

*These authors contributed equally to this work

Correspondence to:

Li Zhu, email: [email protected]

Keywords: NRF1, StAR, testosterone synthesis, hypoxia, Leydig cells

Received: December 01, 2016     Accepted: January 11, 2017     Published: January 27, 2017


Male fertility disorders play a key role in half of all infertility cases. Reduction in testosterone induced by hypoxia might cause diseases in reproductive system and other organs. Hypoxic exposure caused a significant decrease of NRF1. Software analysis reported that the promoter region of steroidogenic acute regulatory protein (StAR) contained NRF1 binding sites, indicating NRF1 promoted testicular steroidogenesis. The purpose of this study is to determine NRF1 is involved in testosterone synthesis; and under hypoxia, the decrease of testosterone synthesis is caused by lower expression of NRF1. We designed both in vivo and in vitro experiments. Under hypoxia, the expressions of NRF1 in Leydig cells and testosterone level were significantly decreased both in vivo and in vitro. Overexpression and interference NRF1 could induced StAR and testosterone increased and decreased respectively. ChIP results confirmed the binding of NRF1 to StAR promoter region. In conclusion, decline of NRF1 expression downregulated the level of StAR, which ultimately resulted in a reduction in testosterone synthesis.

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