Old Chemicals New Risks: Environmental Pollutants Directly Interfere with Several Cellular Receptor Pathways

The newest blog post from Ingemar Pongratz:

Different environmental contaminants have long been known to interfere with hormonal signaling in humans and all kinds of animals, causing reproductive and developmental problems and diseases such as cancer.  One such group of chemical contaminants act through activation of an intracellular receptor named the aryl hydrocarbon receptor (AhR). This receptor has a unique ability to bind to a wide range of compounds released into the environment through various industrial processes and incomplete combustion of household and industrial waste. Examples include dioxins, polychlorinated biphenyls, and several groups of polyaromatic hydrocarbons present in household plastics. The activated AhR influences the expression rate of a wide range of gene networks in response to binding any of these compounds, through direct binding to DNA regulatory elements.

One hormonal pathway that is affected by dioxins, and related compounds, is estrogen signaling. Estrogens are of vital importance for proper function of the female reproductive organs, but also influences brain function, bone health and vascular function in both males and females. The physiological effects of estrogens are mediated by two intracellular receptor proteins, the estrogen receptors α and β (ERα and ERβ). Dioxins and a number of related compounds have been shown to interfere with estrogen signaling in several species, including humans, causing infertility or reproductive abnormalities, cancer, osteoporosis and cardiovascular disease. The mechanism behind this interference has until recently remained largely unknown, but has been presumed to be mediated by the AhR.

In this publication we presented evidence for an overlap in compound recognition between the AhR and ERα and ERβ where the two types of receptors are able to bind to a common chemical, 3-methylcolanthrene (3-MC), a combustion byproduct classified as a potent carcinogen in humans. 3-MC was shown to be almost as potent as estrogens in promoting activity of estrogen regulated genes. In contrast, TCDD (a dioxin with high affinity for the AhR) did not induce a similar estrogen-like activity, showing that the AhR did not influence the activity of the ERs.

Physiological estrogen production and resultant gene activity is a tightly regulated process in a healthy human or animal, and the improper activation of the ERs through a chemical present in the environment could cause imbalances that may negatively affect individual health both in the short and long term perspective.

The unrestricted release of these chemicals during the last five to seven decades has resulted in an environmental burden so serious, that these days, humans are exposed to these chemicals on a daily basis from so many sources that reproductive ability and overall health may be compromised even before birth!

Swedenborg et al Molecular Pharmacology 2008. Sid 575-586

via Ingemar Pongratz http://ingemarpongratz.se/old-chemicals-new-risks-environmental-pollutants-directly-interfere-with-several-cellular-receptor-pathways/


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