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Recent advances in the study of testicular nuclear receptor 4

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Abstract

Testicular nuclear receptor 4 (TR4), also known as NR2C2 (nuclear receptor subfamily 2, group C, member 2), is a transcriptional factor and a member of the nuclear receptor family. TR4 was initially cloned from human and rat hypothalamus, prostate, and testes libraries. For almost two decades, its specific tissue distribution, genomic organization, and chromosomal assignment have been well investigated in humans and animals. However, it has been very difficult to study TR4’s physiological functions due to a lack of specific ligands. Gene knock-out animal techniques provide an alternative approach for defining the biological functions of TR4. In vivo studies of TR4 gene knockout mice (TR4 −/−) found that they display severe spinal curvature, subfertility, premature aging, and prostate prostatic intraepithelial neoplasia (PIN) development. Upstream modulators, downstream target gene regulation, feedback mechanisms, and differential modulation mediated by the recruitment of other nuclear receptors and coregulators have been identified in studies using the TR4 −/− phenotype. With the establishment of a tissue-specific TR4 −/− mouse model, research on TR4 will be more convenient in the future.

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Authors and Affiliations

  1. Department of Urology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China

    Xian-fan Ding, Shi-cheng Yu, Bi-de Chen & Gong-hui Li

  2. George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester, New York, 14642, USA

    Shin-jen Lin & Chawnshang Chang

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  1. Xian-fan Ding
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  2. Shi-cheng Yu
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  3. Bi-de Chen
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  4. Shin-jen Lin
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  5. Chawnshang Chang
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  6. Gong-hui Li
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Correspondence to Chawnshang Chang or Gong-hui Li.

Additional information

Project supported by the National Natural Science Foundation of China (No. 30973001), the National Basic Research Program (973) of China (No. 2012CB518304), the Zhejiang Provincial Natural Science Foundation of China (No. Y2110446), the Qianjiang Talents Project of Zhejiang Province (No. 2011R10039), and the PAO Yu-kong International Foundation for Scholars and Scientists, China

Dr. Chawnshang CHANG is a George Hoyt Whipple Distinguished Professor of Pathology in University of Rochester, USA. He earned his PhD degree from the University of Chicago, USA in 1985. In 1988, Dr. CHANG succeeded in becoming the first scientist to clone the complete human and rat androgen receptors (AR). It is the landmark discovery in the Androgen-AR field. Over the next 25 years, he continued his research on AR and three nuclear orphan receptors TR2, TR3, and TR4 he isolated from human testis, and had more than 350 papers published, including Science, Nature, and so on.

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Ding, Xf., Yu, Sc., Chen, Bd. et al. Recent advances in the study of testicular nuclear receptor 4. J. Zhejiang Univ. Sci. B 14, 171–177 (2013). https://doi.org/10.1631/jzus.B1200357

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