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Endocrine-disrupting potentials of equine estrogens equilin, equilenin, and their metabolites, in the medaka Oryzias latipes: in silico and DNA microarray studies.

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Endocrine-disrupting potentials of equine estrogens equilin, equilenin, and their metabolites, in the medaka Oryzias latipes: in silico and DNA microarray studies.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Uchida, Masaya Ishibashi, Hiroshi Yamamoto, Ryoko Koyanagi, Akiko Kusano, Teruhiko Tominaga, Nobuaki Ishibashi, Yasuhiro Arizono, Koji
Description	Country affiliation: Japan Author Affiliation: Uchida M ( Mizuki biotech, Co., Ltd, 1-1 Hyakunenkouen, Kurume, Fukuoka, 839-0864, Japan.); Ishibashi H ( Department of Food and Nutrition, Shokei University Junior College, 2-6-78 Kuhonji, Kumamoto, 862-8678, Japan.); Yamamoto R ( Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, 3-1-100 Tsukide, Kumamoto, 862-8502, Japan.); Koyanagi A ( Mizuki biotech, Co., Ltd, 1-1 Hyakunenkouen, Kurume, Fukuoka, 839-0864, Japan.); Kusano T ( Mizuki biotech, Co., Ltd, 1-1 Hyakunenkouen, Kurume, Fukuoka, 839-0864, Japan.); Tominaga N ( Department of Chemical and Biological Engineering, Ariake National College of Technology, 150 Higashi-hagio-machi, Omuta, Fukuoka, 836-8585, Japan.); Ishibashi Y ( Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, 3-1-100 Tsukide, Kumamoto, 862-8502, Japan.); Arizono K ( Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, 3-1-100 Tsukide, Kumamoto, 862-8502, Japan.)
Abstract	Although several previous studies have demonstrated the presence of equine estrogens in the aquatic environment, limited data are currently available on the endocrine-disrupting potentials in fish and the risks they pose to aquatic organisms. To investigate the interactions of major equine estrogens equilin (Eq) and equilenin (Eqn), as well as their metabolites 17 -dihydroequilin, 17ß-dihydroequilin, 17 -dihydroequilenin and 17ß-dihydroequilenin, with the estrogen receptor (ER ) of medaka (Oryzias latipes), a three-dimensional model of the ligand-binding domain (LBD) of ER was built in silico, and docking simulations were performed. The docking simulation analysis indicated that the interaction of 17ß-dihydroequilenin with the ER LBD is the most potent, followed by those of 17 -dihydroequilin and 17ß-dihydroequilin, whereas those of Eq and Eqn were least potent. We further analyzed gene expression profiles in the livers of male medaka exposed to Eq and Eqn. A DNA microarray representing 6000 genes revealed that 24-h exposure to Eq and Eqn (100 ng/L) upregulated the expression of 6 and 34 genes in the livers of males, respectively. Genes upregulated by Eq included the estrogenic biomarker genes vitellogenins and choriogenins, suggesting the estrogenic potential of Eq. In contrast, Eqn exposure upregulated several cancer-related genes, such as mediator complex subunit 16 and RAS oncogene family members, suggesting a carcinogenic potential for Eqn. These results suggest that equine estrogens may have not only endocrine-disrupting potentials via the ER signaling pathway but also carcinogenic potency in male medaka.
File Format	HTM / HTML
ISSN	0260437X
Issue Number	9
Volume Number	35
e-ISSN	10991263
Journal	Journal of Applied Toxicology
Language	English
Publisher	Wiley
Publisher Date	2015-09-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Toxicology Endocrine Disruptors Toxicity Equilenin Equilin Liver Drug Effects Oryzias Metabolism Water Pollutants, Chemical Animals Estrogen Receptor Alpha Estrogen Receptor Beta Ligands Male Molecular Docking Simulation Oligonucleotide Array Sequence Analysis Protein Binding Transcriptome Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Toxicology

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Gene expression analyses of vitellogenin, choriogenin and estrogen receptor subtypes in the livers of male medaka (Oryzias latipes) exposed to equine estrogens.

Transcriptional responses in Japanese medaka (Oryzias latipes) exposed to binary mixtures of an estrogen and anti-estrogens.

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Endocrine-disrupting potentials of equine estrogens equilin, equilenin, and their metabolites, in the medaka Oryzias latipes: in silico and DNA microarray studies.

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