## Endocrine disruptors act via several mechanisms

A more deep examination of endocrine disruptors revealed that they can act through several mechanisms. The first is to mimic the function of hormones, where an endocrine disruptor causes that the body responses like to a natural hormone. In this case, the body reacts in two ways. Either there is an exaggerated response to the stimulus, e.g., excessive muscle mass is produced when growth hormones are used, or there is a response to the stimulus at an inappropriate time. An example of such a response is the production of insulin by the beta cells of the pancreas when it is not needed, resulting in a deregulation of blood glucose levels. Another way to disrupt the endocrine system is to block the action of a hormone by binding to its receptor (Figure 12.2). Both the hormone and the endocrine disruptor have a certain binding strength (affinity) to this receptor, which can be higher or lower for the endocrine disruptor than for the natural hormone. If the affinity of the EDC is higher than the hormone, the disruptor displaces the hormone from binding to the receptor. However, if the EDC affinity is lower, the endocrine disruptor may bind preferentially because its concentration is high enough to simply "displace" the hormone from binding. For example, bisphenol A, which is the basic building element of many plastic products, can act in this way. The final mechanism of action of endocrine disruptors is the direct stimulation or inhibition of the endocrine system by altering hormone levels in the body. Accordingly, the body's response is strengthened or weakened, cellular signalling is altered and thus the expression of genes is influenced. The consequence of this effect of endocrine disruptors can be the early onset of puberty, changes in brain development, behavioural changes or cancer development.

The defining characteristic of endocrine disruptors is the triggering of harmful effects in the organism. However, it should be emphasised that humans are more susceptible to endocrine effects during important stages of development (namely during in utero development or during early childhood). It is also an important fact that the same amount of an endocrine disruptor can affect and harm a developing foetus but have little or no impact on the mother's body. This is because a foetus is more sensitive to chemical agents due to the intense and ongoing cell division and differentiation processes, and therefore internal homeostasis can be more easily disturbed. An example of a harmful or destructive effect of hormone disruption is diethylstilbestrol (DES). Diethylstilbestrol is a synthetic oestrogen that was used from the 1940s to the early 1970s for hormonal problems in a pregnant woman or women approaching early onset menopause. The drug helped to prevent spontaneous abortions and to support the growth of the foetus. Its use was banned after it was discovered that children exposed to DES during intrauterine development had an increased incidence of post-pubertal and pubertal cancers. In girls, it was vaginal cancer, in boys, to a lesser extent, prostate cancer. However, before the negative effect of this substance was discovered, the drug was prescribed to up to 5 million women around the world.

It is important to emphasise that the consequence of the action of endocrine disruptors is a (hormonal) imbalance or disruption of certain processes that can lead to the development of various diseases (Figure 12.3). In addition to cancer, these diseases include type 2 diabetes and various other metabolic syndromes (e.g., obesity), as well as impaired reproductive ability (which can lead to reduced fertility or infertility), disorders of brain development or impaired cognitive abilities (which can manifest themselves, for example, in the development of neurodegenerative diseases or learning disorders) or disorders of the immune system and congenital defects. The common features that precede the onset of all these diseases are defective cell signalling and changes in the expression of key genes involved in the control of individual processes in the body.