Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression.
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.
Department of Biochemistry, Institute for Nautical Medicine, Nantong University, China.
Xueting
X
Wang
Department of Rehabilitation of the Six People's Hospital of Nantong, Jiangsu, China.
Longlu
L
Pan
Department of Biochemistry, Institute for Nautical Medicine, Nantong University, China.
Zhiran
Z
Zou
Department of Biochemistry, Institute for Nautical Medicine, Nantong University, China.
Dan
D
Wang
Department of Biochemistry, Institute for Nautical Medicine, Nantong University, China.
Yapeng
Y
Lu
Co-Innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
Zhangji
Z
Dong
Department of Biochemistry, Institute for Nautical Medicine, Nantong University, China.|Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, China.
Li
L
Zhu
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D015536:Down-Regulation; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051266:Nuclear Respiratory Factor 1 / Q000096:biosynthesis / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D013739:Testosterone / Q000096:biosynthesis*; D014162:Transfection; D000098682:Steroidogenic Acute Regulatory Protein
C495634:Nrf1 protein, mouse; D051266:Nuclear Respiratory Factor 1; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone
Leydig cells; NRF1; StAR; hypoxia; testosterone synthesis