Of the contaminants occurring in our environment and food, the toxicologically most significant group are substances known as persistent organic pollutants (POP). As the name suggests, they are chemicals that persist in nature for a long time and tend to accumulate in the food chain.
Dioxins constitute one key POP group. There are a large number of dioxin derivatives, of which the most toxic (especially TCDD) engender already at very small exposures an exceptionally high number of various biochemical and toxic responses in laboratory animals. In humans, their biological half-life is extremely long (several years), and there is epidemiological evidence of a potential link between dioxins and a number of adverse health effects, of which a drop in sperm concentration in semen occurs at the lowest exposure level. In that regard, the mean exposure on the population level currently exceeds the tolerable upper intake level broadly across Europe, even though background levels of dioxin have decreased markedly in the past 30 years.
While dioxins are among the most extensively investigated contaminant chemicals in the world, knowledge of their mechanisms of toxicity remains insufficient. What is known is that the AH (aryl hydrocarbon) receptor (AHR) is needed to mediate their effects. AHR is a transcription factor that is activated when ligands, such as dioxins, bind with it, after which the receptor alters the expression of the genes it regulates. AHR is an evolutionarily well-conserved protein molecule that dates back more than 600 million years, whose physiological effects have only recently started to be uncovered. It has proven to be a key immune response regulator and a protector of the integrity of bodily interfaces. AHR has also been found to contribute to the growth of several organs and tissues, the differentiation of stem cells, the adaptation of the circadian rhythm, the maintenance of disease tolerance and the development of obesity.
At the department, we are currently investigating AHR’s role in energy balance as well as interaction between AHR and retinoids. Our research findings shed new light on the physiological duties of AHR and increase understanding of the mechanisms of toxicity of dioxins and other chemicals whose effect is mediated by AHR.