Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor.

Article Details

Citation

Copy to clipboard

Takeuchi S, Iida M, Kobayashi S, Jin K, Matsuda T, Kojima H

Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor.

Toxicology. 2005 Jun 1;210(2-3):223-33.

PubMed ID

15840436 [ View in PubMed

]

Abstract

Some phthalates are suspected to disrupt the endocrine system, especially by mimicking estrogens. In this study, we characterized the activities of human estrogen receptor alpha (hERalpha), human estrogen receptor beta (hERbeta), and human androgen receptor (hAR) in the presence of 22 phthalates including 3 of their metabolites using highly sensitive reporter gene assays. Of the 22 compounds tested, several phthalate diesters with alkyl chains ranging in length from C3 to C6 exhibited not only hERalpha-mediated estrogenic activity, but also hERbeta-mediated antiestrogenic activity in a dose-dependent manner. In addition, we found that some phthalate diesters possess hAR-mediated antiandrogenic activity. However, the phthalates having side chains with very short length (diethyl) or very long length (diheptyl), and three metabolites (monoesters) were found to have no effect on the activities of the three receptors. These results indicate that several phthalate esters simultaneously act as agonists and/or antagonists via one or more hormonal receptors, and interaction of phthalate esters with the estrogen and androgen receptors requires certain size and bulkiness with alkyl groups.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Phthalic Acid	Estrogen receptor beta	Protein	Humans	Unknown	Not Available	Details