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Induction of cytochrome P450-1A by the equine estrogen equilenin, a new endogenous aryl hydrocarbon receptor ligand

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Title: Induction of cytochrome P450-1A by the equine estrogen equilenin, a new endogenous aryl hydrocarbon receptor ligand
Authors: Jinno, Asumi Browse this author
Maruyama, Yutaka Browse this author
Ishizuka, Mayumi Browse this author →KAKEN DB
Kazusaka, Akio Browse this author →KAKEN DB
Nakamura, Akio Browse this author
Fujita, Shoichi6 Browse this author →KAKEN DB
Authors(alt): 藤田, 正一6
Keywords: Steroid hormone
Aryl hydrocarbon receptor
Issue Date: Jan-2006
Publisher: Elsevier
Journal Title: The Journal of Steroid Biochemistry and Molecular Biology
Volume: 98
Issue: 1
Start Page: 48
End Page: 55
Publisher DOI: 10.1016/j.jsbmb.2005.07.003
PMID: 16191477
Abstract: Equilenin is one of 10 kinds of estrogens that are found in pregnant mares’ urine. It has been used extensively for estrogen replacement therapy in postmenopausal women. Typical inducers of the cytochrome P4501A1 (CYP1A1), such as TCDD, benzo(a)pyrene (B(a)P) and 3-methylcholanthrene, have a planar molecular structure in common and bind to the aryl hydrocarbon receptor (AhR). The structure of equilenin differs from classic estrogens by the presence of two additional double bonds in ring B of the steroid nucleus, and it is planar. This structural similarity of equilenin to the typical AhR agonist prompted us to investigate the capability of equilenin to induce CYP1A1 expression. Administration of equilenin to two mouse strains (C57BL and DBA) that exhibit different degrees of responsiveness to an Ah-receptor agonist and showed that equilenin was capable of dose-dependently increasing both the ethoxyresorufin O-deethylase activity and CYP1a proteins in both strains of mice. Equilenin also induced CYP1A1 mRNA in treated HepG2 cell lines and transcriptional activity in an XRE-directed luciferase reporter gene. Competitive binding studies using C57BL AhR indicated equilenin weakly displaced 3H-B(a)P from AhR. Together, these data show that equilenin, an equine steroid hormone, served as an AhR ligand in the present study.
Type: article (author version)
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 藤田 正一

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