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Aryl hydrocarbon receptor activation leads to impairment of estrogen-driven chicken vitellogenin promoter activity in LMH cells

Bussmann, Ursula A., Pérez Sáez, Juan M., Bussmann, Leonardo E., Barañao, J. Lino
Comparative Biochemistry and Physiology, Part C 2013 v.157 pp. 111-118
agonists, chickens, estradiol, estrogen receptors, fish, genes, hepatocytes, hepatoma, liver, models, physiology, pollution, promoter regions, toxicity, transcription factors, vitellogenin
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates most of the toxic effects of environmental contaminants. Among the multiple pleiotropic responses elicited by AHR agonists, the antiestrogenic and endocrine-disrupting action of the receptor activation is one of the most studied. It has been demonstrated that some AHR agonists disrupt estradiol-induced vitellogenin synthesis in the fish liver via a mechanism that involves crosstalk between the AHR and the estrogen receptor (ER). Chicken hepatocytes have become a model for the study of AHR action in birds and the induction of the signal and its effect in these cells are well established. However, the impact of AHR activation on estradiol-regulated responses in the chicken liver remains to be demonstrated. The aim of the present study was, therefore, to determine the effect of AHR action on ER-driven transcription in a convenient model of chicken liver cells. For this purpose, we designed a reporter construct bearing the 5′ regulatory region of the chicken vitellogenin II gene and used it to transfect chicken hepatoma LMH cells. We found that β-naphthoflavone represses ER-driven vitellogenin promoter activity and that this action is mediated by the AHR. This inhibitory crosstalk between both pathways appears to be unidirectional, since estradiol did not alter the transcript levels of an AHR target gene. Besides, and highly relevant, we show that LMH cell line transfected with a reporter construct bearing the chicken vitellogenin promoter sequence is a useful and convenient model for the study of AHR–ER interaction in chicken liver-derived cells.