Untersuchung des Zusammenspiels zwischen Estrogenrezeptoren und AhR nuclear translocator (ARNT).

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Estrogens are steroid hormones and regulate many vital physiological processes. Their effects are mediated by two estrogen receptors (ER), ER¿ and ERß which regulate expression of target genes following binding of the ligand. Contaminants in the environment can interfere with the function of ERs and thereby cause deleterious effects in the body. One such contaminant is dioxin which is an environmental pollutant formed through incomplete combustion of waste. The biological effects of dioxin are mediated by the Aryl hydrocarbon receptor (AhR) that belongs to the family of basic helix-loop-helix (bHLH)-PAS transcriptional regulators. To become active, AhR must not only bind to dioxin but additionally to its partner AhR nuclear translocator (ARNT), another bHLH-PAS protein. Recently, it has been shown that ARNT can also act as co-activator of ER, i.e. increased amounts of ARNT enhance ER activity. This finding suggests that the interference of dioxin with the ER function is at least partly due to a competition between ER and AhR for the common co-activator ARNT. The aim of this project is to investigate this hypothesis by elucidating the interplay between ARNT and ER. This should be achieved by firstly testing whether ARNT up- and down-regulation affects the effects of dioxin on ER function, and secondly investigating the involvement of additional factors in the ARNT-ER interplay, namely other co-activators of ER. This should lead to a better understanding of the harmful effects of dioxin and might broaden our knowledge about the action of environmental contaminants in general.