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Frontiers in Genetics

Systems Endocrinology

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00505

Testosterone Deficiency Caused by Castration Modulates Mitochondrial Biogenesis through the AR/PGC1α/TFAM Pathway

 Mingzhou Li1*, Can Liu1, JiDeng Ma1, Jinwei Zhang1, Han Zhao1, Yan Zhu1, Jing Qi1, lingyan Liu1, li zhu1,  yanzhi jiang1, Guoqing Tang1 and xuewei li1
  • 1College of Animal Science and Technology, Sichuan Agricultural University, China

Mammalian mitochondrial biogenesis is a complex process involving mitochondrial proliferation and differentiation. Mitochondrial DNA transcription factor A (TFAM), which encodes a major component of a protein-mitochondrial DNA (mtDNA) complex, is regulated by peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α). Testosterone is the primary male sex hormone and plays an increasingly important role in mammalian development through its interaction with androgen receptor (AR). However, the function of AR in mitochondrial biogenesis induced by testosterone deficiency has not been investigated. Here we explored the molecular mechanism underlying the effect of testosterone deficiency on mitochondrial biogenesis using a Yorkshire boar model. Testosterone deficiency caused by castration induced changes in mtDNA copy numbers in various tissues, and AR showed the opposite tendency to that of mtDNA copy number, particularly in adipose tissues and muscle tissues. In addition, castration weakened the correlation of PGC1α and mtDNA copy number, while AR and TFAM showed a relatively high correlation in both control and castrated pigs. Furthermore, luciferase assays revealed that AR binds to potential AR elements in the TFAM promoter to promote TFAM expression. Taken together, testosterone may be involved in the pathway linking PGC1α to mitochondrial biogenesis through the interaction between AR and TFAM.

Keywords: mitochondrial biogenesis, Testosterone, androgen receptor, TFAM, Castration

Received: 08 Feb 2019; Accepted: 07 May 2019.

Edited by:

Louise Metherell, Queen Mary University of London, United Kingdom

Reviewed by:

Rodolfo A. Rey, Center for Endocrinology Research "Dr. César Bergadá "(CEDIE), Argentina
Laura Ellestad, University of Georgia, United States  

Copyright: © 2019 Li, Liu, Ma, Zhang, Zhao, Zhu, Qi, Liu, zhu, jiang, Tang and li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Mingzhou Li, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China, mingzhou.li@sicau.edu.cn