Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor

Abstract Prostate cancer is a major cause of death in males. Cyproterone acetate (CPA), the steroidal anti-androgen for part of androgen deprivation therapy, may block the androgen-receptor interaction and then reduce serum testosterone through its weak anti-gonadotropic action. In addition to CPA i...

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Autores principales:	Chih-Shou Chen, Guan-Lun Gao, Dong-Ru Ho, Chih-Yi Lin, Yu-Ting Chou, Shan-Chun Chen, Min-Cong Huang, Wen-Ya Kao, Jyan-Gwo Joseph Su
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78b4189db5554d3684b3a82e42a3a9a9
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spelling	oai:doaj.org-article:78b4189db5554d3684b3a82e42a3a9a92021-12-02T13:35:03ZCyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor10.1038/s41598-021-84769-72045-2322https://doaj.org/article/78b4189db5554d3684b3a82e42a3a9a92021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84769-7https://doaj.org/toc/2045-2322Abstract Prostate cancer is a major cause of death in males. Cyproterone acetate (CPA), the steroidal anti-androgen for part of androgen deprivation therapy, may block the androgen-receptor interaction and then reduce serum testosterone through its weak anti-gonadotropic action. In addition to CPA inducing hepatitis, CPA is known to cause liver tumors in rats also. Aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor and regulates multiple physiological functions. CYP1A1 is an AhR-targeted gene. We found that CPA induced CYP1A1 expression, transcriptional activity of the aryl hydrocarbon response element (AHRE), and the nuclear localization of AhR in mouse Hepa-1c1c7 cells. However, CPA suppressed CYP1A1 mRNA expression and the transcriptional activity of AHRE in human HepG2 and MCF7 cells, and also decreased AhR ligand-induced CYP1A1 protein expression and transcriptional activity of AHRE in HepG2 cells. In summary, CPA is an AhR agonist in mouse cells, but an AhR antagonist in human cells. Accordingly, CPA potentially plays a role as an endocrine disruptor of the AhR. This study helps us to understand why CPA induces acute hepatitis, gene mutation, and many other side effects. In addition, it may trigger further studies investigating the relationships between CPA, glucocorticoid receptor and castration-resistant prostate cancer in the future.Chih-Shou ChenGuan-Lun GaoDong-Ru HoChih-Yi LinYu-Ting ChouShan-Chun ChenMin-Cong HuangWen-Ya KaoJyan-Gwo Joseph SuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chih-Shou Chen Guan-Lun Gao Dong-Ru Ho Chih-Yi Lin Yu-Ting Chou Shan-Chun Chen Min-Cong Huang Wen-Ya Kao Jyan-Gwo Joseph Su Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor
description	Abstract Prostate cancer is a major cause of death in males. Cyproterone acetate (CPA), the steroidal anti-androgen for part of androgen deprivation therapy, may block the androgen-receptor interaction and then reduce serum testosterone through its weak anti-gonadotropic action. In addition to CPA inducing hepatitis, CPA is known to cause liver tumors in rats also. Aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor and regulates multiple physiological functions. CYP1A1 is an AhR-targeted gene. We found that CPA induced CYP1A1 expression, transcriptional activity of the aryl hydrocarbon response element (AHRE), and the nuclear localization of AhR in mouse Hepa-1c1c7 cells. However, CPA suppressed CYP1A1 mRNA expression and the transcriptional activity of AHRE in human HepG2 and MCF7 cells, and also decreased AhR ligand-induced CYP1A1 protein expression and transcriptional activity of AHRE in HepG2 cells. In summary, CPA is an AhR agonist in mouse cells, but an AhR antagonist in human cells. Accordingly, CPA potentially plays a role as an endocrine disruptor of the AhR. This study helps us to understand why CPA induces acute hepatitis, gene mutation, and many other side effects. In addition, it may trigger further studies investigating the relationships between CPA, glucocorticoid receptor and castration-resistant prostate cancer in the future.
format	article
author	Chih-Shou Chen Guan-Lun Gao Dong-Ru Ho Chih-Yi Lin Yu-Ting Chou Shan-Chun Chen Min-Cong Huang Wen-Ya Kao Jyan-Gwo Joseph Su
author_facet	Chih-Shou Chen Guan-Lun Gao Dong-Ru Ho Chih-Yi Lin Yu-Ting Chou Shan-Chun Chen Min-Cong Huang Wen-Ya Kao Jyan-Gwo Joseph Su
author_sort	Chih-Shou Chen
title	Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor
title_short	Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor
title_full	Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor
title_fullStr	Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor
title_full_unstemmed	Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor
title_sort	cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/78b4189db5554d3684b3a82e42a3a9a9
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Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor

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