Dioxins, the aryl hydrocarbon receptor and the central regulation of energy balance.
Dioxins are ubiquitous environmental contaminants that have attracted toxicological interest not only for the potential risk they pose to human health but also because of their unique mechanism of action. This mechanism involves a specific, phylogenetically old intracellular receptor (the aryl hydrocarbon receptor, AHR) which has recently proven to have an integral regulatory role in a number of physiological processes, but whose endogenous ligand is still elusive. A major acute impact of dioxins in laboratory animals is the wasting syndrome, which represents a puzzling and dramatic perturbation of the regulatory systems for energy balance. A single dose of the most potent dioxin, TCDD, can permanently readjust the defended body weight set-point level thus providing a potentially useful tool and model for physiological research. Recent evidence of response-selective modulation of AHR action by alternative ligands suggests further that even therapeutic implications might be possible in the future.
Lindén
Jere
J
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Finland.
Lensu
Sanna
S
Tuomisto
Jouko
J
Pohjanvirta
Raimo
R
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004147:Dioxins / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects*; D004785:Environmental Pollutants / Q000032:analysis / Q000378:metabolism; D005260:Female; D005506:Food Contamination / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D019282:Wasting Syndrome / Q000139:chemically induced / Q000378:metabolism
D004147:Dioxins; D004785:Environmental Pollutants; D018336:Receptors, Aryl Hydrocarbon