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Mechanisms of endocrine disruption
A endocrine disrupting chemical can affect the endocrine system of an organism in a wide variety of ways. Here are some of them, particularly focusing on sex hormone disrupters:
1) Binding and activating the oestrogen receptor (therefore acting as an oestrogen)
By imitating the female hormone 17beta-oestradiol.
One complexity of this mode of action is the fact that there
are a variety of oestrogen receptors, present in a wide range
of tissues.
It has been found that if several chemicals that can bind and
activate the oestrogen receptor are added together, their effects
will usually be additive, so the effects of small quantities
of a range of oestrogenic chemicals can add together into a much
larger effect (Soto et al., 1995). In addition, chemicals such
as butylbenzyl phthalate and di-n-butyl phthalate have been shown
to add their effects to any natural oestrogen present (Jobling
et al., 1995).
It is also possible that some chemicals will demonstrate more
than additive effects, they will demonstrate synergism.
It is unlikely that synergism will occur with two chemicals acting
through one receptor; the one paper that claimed to show this
effect was later withdrawn (McLachlan, 1997). However, synergism
is known to occur in other areas of toxicology when the two chemicals
are working through different mechanisms, for example tobacco
smoking accentuates the toxicity of many chemicals.
2) Binding but not activating the oestrogen receptor (therefore acting as an anti-oestrogen)
3) Binding other receptors
There are many other receptors involved in the hormonal system, for example the androgen receptors for male hormones. This binding can either activate the receptor, or inactivate it, as happens with anti-androgens like the DDT metabolite p, p'-DDE (see the DDT page).
4) Modifying the metabolism of natural hormones
Some chemicals, such as lindane and atrazine,
can effect the metabolic pathway of oestradiol, producing more
oestrogenic metabolites (see the DDT page).
Other chemicals activate enzymes which speed up the metabolism
of hormones, so disrupting their natural state.
The testes contain specific enzymes to metabolise oestrogens
(Toppari et al., 1996). These enzymes break down oestrogen rapidly
to a form where they can no longer bind their receptor. However,
if this enzyme is affected by a xenoestrogen, this metabolism
will be reduced, increasing the exposure of the testes to oestrogen.
This could be particularly relevant during foetal development,
when there are high levels of oestrogens (Toppari et al., 1996).
5) Modifying the number of hormone receptors in a cell
Complex mechanisms control the numbers of hormone receptors present in cells. A chemical could reduce or increase the number of receptors, and so affect the extant of response to natural or artificial hormones.
6) Modifying the production of natural hormones
Chemicals can affecting natural hormone production by interfering in other signalling systems, such as other hormone systems like the thyroid system, or the immune and nervous systems.