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Huang Fuyan, Chen Qinchang, Tan Haoyue, Guo Jing, Yu Nanyang, Shi Wei, Yu Hongxia. Review on the Effects of Endocrine Disrupting Chemicals on Dimerization of Nuclear Receptors[J]. Asian Journal of Ecotoxicology, 2021, 16(4): 17-31. doi: 10.7524/AJE.1673-5897.20201105004
Citation: Huang Fuyan, Chen Qinchang, Tan Haoyue, Guo Jing, Yu Nanyang, Shi Wei, Yu Hongxia. Review on the Effects of Endocrine Disrupting Chemicals on Dimerization of Nuclear Receptors[J]. Asian Journal of Ecotoxicology, 2021, 16(4): 17-31. doi: 10.7524/AJE.1673-5897.20201105004
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Review on the Effects of Endocrine Disrupting Chemicals on Dimerization of Nuclear Receptors

  • State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China

  • Corresponding author: Yu Nanyang, yuny@nju.edu.cn ; 
  • Received Date: 05/11/2020
    Accepted Date: 29/12/2020
    Fund Project:
  • Many environmental chemicals can mediate nuclear receptor (NR), causing endocrine disrupting effects on human. Endocrine disrupting chemicals (EDCs) can bind NR as a ligand by imitating or antagonizing natural hormones to form NR-ligand complex. The complex as homodimer or heterodimer in the nucleus, ultimately regulating transcription activity through the recruitment of coregulators. At present, studies on EDCs mainly focus on the process of NR-ligand binding, while few concentrate on nuclear receptor dimerization. The dimerization of NR plays a decisive role in transcription activity, and blocking the dimerization process will cause transcription inactivation. The effects of EDCs on dimerization of nuclear receptors are different. Only the agonist can promote the homodimerization of androgen receptor (AR), while estrogen receptor (ER) can induce the formation of ER dimer after binding with agonists or antagonists, but the dimerization types are different. Searching ToxCast and Tox21 databases, it is found that up to 227 EDCs can induce dimerization of estrogen receptor (ER). Compared with ERα-ERα homodimer (6.09%～7.38% active rate), EDCs are more likely to induce ERα-ERβ heterodimer (11.25%～12.22% active rate) and ERβ-ERβ homodimer (10.02%～11.69% active rate). EDCs can also differentially induce the formation of heterodimer between other nuclear receptors such as vitamin D receptor (VDR) and retinoid X receptor (RXR). Different dimers are of great significance for studying the physiological correlation of transcription activity of EDCs. Based on the reference chemicals reported by OECD, it is found that there is a better correlation between dimerization activity and transcription activity than NR-ligand binding. In this paper, the effects of EDCs on NR dimerization are summarized from three aspects: the transcription mechanism of NR dimerization mediated by EDCs, the relationship between NR dimerization and transcription activity, and the research methods of NR dimerization, in order to provide reference for an in-depth understanding of the molecular mechanism and the promotion of risk assessment of EDCs.
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Review on the Effects of Endocrine Disrupting Chemicals on Dimerization of Nuclear Receptors

  • Received Date: 05/11/2020
  • Accepted Date: 29/12/2020
Fund Project:

Abstract: Many environmental chemicals can mediate nuclear receptor (NR), causing endocrine disrupting effects on human. Endocrine disrupting chemicals (EDCs) can bind NR as a ligand by imitating or antagonizing natural hormones to form NR-ligand complex. The complex as homodimer or heterodimer in the nucleus, ultimately regulating transcription activity through the recruitment of coregulators. At present, studies on EDCs mainly focus on the process of NR-ligand binding, while few concentrate on nuclear receptor dimerization. The dimerization of NR plays a decisive role in transcription activity, and blocking the dimerization process will cause transcription inactivation. The effects of EDCs on dimerization of nuclear receptors are different. Only the agonist can promote the homodimerization of androgen receptor (AR), while estrogen receptor (ER) can induce the formation of ER dimer after binding with agonists or antagonists, but the dimerization types are different. Searching ToxCast and Tox21 databases, it is found that up to 227 EDCs can induce dimerization of estrogen receptor (ER). Compared with ERα-ERα homodimer (6.09%～7.38% active rate), EDCs are more likely to induce ERα-ERβ heterodimer (11.25%～12.22% active rate) and ERβ-ERβ homodimer (10.02%～11.69% active rate). EDCs can also differentially induce the formation of heterodimer between other nuclear receptors such as vitamin D receptor (VDR) and retinoid X receptor (RXR). Different dimers are of great significance for studying the physiological correlation of transcription activity of EDCs. Based on the reference chemicals reported by OECD, it is found that there is a better correlation between dimerization activity and transcription activity than NR-ligand binding. In this paper, the effects of EDCs on NR dimerization are summarized from three aspects: the transcription mechanism of NR dimerization mediated by EDCs, the relationship between NR dimerization and transcription activity, and the research methods of NR dimerization, in order to provide reference for an in-depth understanding of the molecular mechanism and the promotion of risk assessment of EDCs.

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