A great deal of substances (contaminants) which we ingest with our food interfere with the hormonal system of humans or animals. This is because they influence the transport, synthesis or metabolism of hormones or interact directly with the hormone receptor, by leading to an effect themselves (agonist) or obstruct the effect of the natural hormone (antagonist).
The "International Programme for Chemical Safety (IPCS)" and other experts describe endocrine disruptors as follows: "An endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism or its progeny, or (sub)populations." (EC, 1999). These disruptors can be of different origins: natural hormones (from humans or animals); synthetic hormones or pharmaceutical substances (contraception, medicinal products, etc.), natural components (mycotoxins, phytoestrogens, etc.), chemical contaminants (phthalates, organotins, pesticides, dioxins, PCBs, flame retardants, etc.).
Many health effects can be attributed to the interaction of these substances with (primarily) nuclear hormone receptors. The best known examples are the receptors of the sex hormones oestrogen and androgen which cause effects on reproduction and fertility. Endocrine disruptors can however also interfere with all sorts of receptors that play a role in cell growth, differentiation, development, homeostasis and metabolism. In case of a disruption, this can lead to proliferative, reproductive and metabolic diseases such as cancer, infertility, obesity or diabetes.
ROLE OF CODA-CERVA
Although eating habits and physical activity are still decisive factors for obesity, increasing attention is being paid to the fact that endocrine disruptors can also play a role. Various mechanisms are known through which endocrine disruptors can contribute to obesity. It has long been known that oestrogens and androgens have an effect on weight. Even more important, however, is the interaction of the Peroxisome proliferator-activated receptor (PRARy) with these endocrine disruptors.
PPARy is the most important regulator of fat development, the activation of which leads to fat cell differentiation (thereby enhancing the glucose intake from the blood). Different agonists for this receptor were linked to weight gain in in vivo studies. Known disruptors via PRARy are tributyltin, triphenyltin and a number of phthalates...
Furthermore, disruption of our thyroid gland or the thyroid system can also lead to weight gain. The thyroid gland and the thyroid receptor (TR) play an important role in central development, basal metabolism, heart activity and homeostasis. Thyroid endocrine disruptors can disrupt the thyroid system at various places (iodium intake, hormone production, hormone intake, conversion between T4 and T3, TR activation and hormone metabolism). This can lead to hypothyroidism or hyperthyroidism. Hypothyroidism refers to a shortage of thyroid hormones T4 and T3. In the foetus this can lead to brain damage and incomplete development, while in adults it can cause primarily cardiovascular diseases. Hyperthyroidism is an overstimulation of the thyroid gland and thus too much T4 and T3, and is associated with accelerated metabolism and enlarged thyroid gland. Known disruptors for the thyroid system are: PCBs, BPA, flame retardants, heavy metals and phthalates.
The focus of our research is on interactions of PPARy and TRb with possible endocrine disruptors (pure or in different food matrices) in our food. A cellular screening system was implemented to that end, namely the chemical-activated luciferase gene expression (CALUX), designed for TRb and PPARy2 (®Bio Detection System, Amsterdam). This is a human cell system in which the receptor in question is transferred safely with a luciferase reporter gene. The agonistic and antagonistic activity of possible endocrine disruptors can be studied in these systems.
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