PMID- 31028793
OWN - NLM
STAT- MEDLINE
DCOM- 20191120
LR  - 20191120
IS  - 1879-1220 (Electronic)
IS  - 0960-0760 (Linking)
VI  - 191
DP  - 2019 Jul
TI  - Transcription regulation of NRF1 on StAR reduces testosterone synthesis in 
      hypoxemic murine.
PG  - 105370
LID - S0960-0760(18)30727-1 [pii]
LID - 10.1016/j.jsbmb.2019.04.019 [doi]
AB  - Male chronic obstructive pulmonary disease (COPD) and sleep apnea patients are 
      associated with serum testosterone level decline because of hypoxemia, resulting 
      in male sexual dysfunction and lower reproductive capacity. Although testosterone 
      replacement therapy used in clinic achieves good results, the side effects 
      indicates that understanding the mechanism followed with targeted treatments are 
      more meaningful. The known mechanism of Hypoxia-inducible factor-1 (HIF-1) 
      mediated steroidogenic acute regulatory protein (StAR) repression did not well 
      explain the reason of hypoxia induced testosterone decline. Our primary results 
      indicated Nuclear respiratory factor 1(NRF1) might be participate in StAR 
      transcription regulation. The study aims to identify the mechanism of the 
      regulation of StAR by NRF1, providing an explanation for the decrease of 
      testosterone induced by hypoxemia. Testosterone level and StAR were determined in 
      COPD model rats, sleep apnea model mice and hypoxia rats (10%O(2)). Results 
      indicated NRF1, StAR and testosterone decreased in testis and ovary and increased 
      in adrenal. Regulation of NRF1 expression under normoxia or hypoxia induced 
      synchronous changes of both StAR and testosterone, indicating the decrease of 
      NRF1 induced StAR repression in hypoxemia were the main cause of serum 
      testosterone decline. The results were confirmed by dual-luciferase reporter 
      assays, regulation of NRF1 synchronously altered the transcriptional activity of 
      StAR. By ChIP, EMSA supershift, NRF1 was found to bind to the Star promoter 
      region. Mutation assays identified two NRF1-binding sites on mouse Star promoter. 
      These findings indicated that NRF1 positivly regulated Star transcription through 
      directly binding to the Star promoter at -1445/-1422 and -44/-19.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Wang, Xueting
AU  - Wang X
AD  - Institute of Special Environmental Medicine, Nantong University, China; 
      Co-innovation Center of Neuroregeneration, Nantong University, China.
FAU - Jin, Liuhan
AU  - Jin L
AD  - Institute of Special Environmental Medicine, Nantong University, China; 
      Co-innovation Center of Neuroregeneration, Nantong University, China.
FAU - Jiang, Shan
AU  - Jiang S
AD  - Institute of Special Environmental Medicine, Nantong University, China; 
      Co-innovation Center of Neuroregeneration, Nantong University, China.
FAU - Wang, Dan
AU  - Wang D
AD  - Institute of Special Environmental Medicine, Nantong University, China; 
      Co-innovation Center of Neuroregeneration, Nantong University, China.
FAU - Lu, Yapeng
AU  - Lu Y
AD  - Institute of Special Environmental Medicine, Nantong University, China; 
      Co-innovation Center of Neuroregeneration, Nantong University, China.
FAU - Zhu, Li
AU  - Zhu L
AD  - Institute of Special Environmental Medicine, Nantong University, China; 
      Co-innovation Center of Neuroregeneration, Nantong University, China. Electronic 
      address: zhuli85051796@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190424
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (Nuclear Respiratory Factor 1)
RN  - 0 (Phosphoproteins)
RN  - 0 (steroidogenic acute regulatory protein)
RN  - 3XMK78S47O (Testosterone)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Hypoxia/genetics/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Nuclear Respiratory Factor 1/*metabolism
MH  - Phosphoproteins/*genetics/metabolism
MH  - Pulmonary Disease, Chronic Obstructive/genetics/metabolism
MH  - Rats, Wistar
MH  - Sleep Apnea Syndromes/genetics/metabolism
MH  - Testosterone/*metabolism
MH  - Transcriptional Activation
OTO - NOTNLM
OT  - Hypoxemia
OT  - NRF 1
OT  - StAR
OT  - Testosterone synthesis
EDAT- 2019/04/28 06:00
MHDA- 2019/11/21 06:00
CRDT- 2019/04/28 06:00
PHST- 2018/11/27 00:00 [received]
PHST- 2019/04/17 00:00 [revised]
PHST- 2019/04/22 00:00 [accepted]
PHST- 2019/04/28 06:00 [pubmed]
PHST- 2019/11/21 06:00 [medline]
PHST- 2019/04/28 06:00 [entrez]
AID - S0960-0760(18)30727-1 [pii]
AID - 10.1016/j.jsbmb.2019.04.019 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2019 Jul;191:105370. doi: 
      10.1016/j.jsbmb.2019.04.019. Epub 2019 Apr 24.