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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will occur with two chemicals acting through one receptor; the one paper that claimed to show this effect was later withdrawn (McLachlan, 1997).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.


This page was last updated in October 1999
Return to the hormone disrupting chemicals home page

References

Jobling, S., Reynolds, T., White, R., Parker, M. G. and Sumpter, J. P. 1995. A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ. Health Persp. 103: 582-587.

McLachlan, J. A. 1997. Synergistic effects of environmental estrogens: Report withdrawn. Science 277: 462-463.

Soto, A. M., Sonnenschein, C., Chung, K. L., Fernandez, M. F., Olea, N. and Serrano, F. O. 1995. The E-SCREEN assay as a tool to identify estrogens: An update on estrogenic environmental pollutants. Environ. Health Persp. 103: 113-122.

Toppari, J., Larsen, J. C., Christiansen, P., Giwercman, A., Grandjean, P., Guillette, L. J., Jégou, B., Jensen, T. K., Jouannet, P., Keiding, N., Leffers, H., McLachlan, J. A., Meyer, O., Müller, J., Rajpert-De Meyts, E., Scheike, T., Sharpe, R., Sumpter, J. and Skakkebaek, N. E. 1996. Male reproductive health and environmental xenoestrogens. Environ. Health Persp. 104 Suppl. 4: 741-803.


URL: http://website.lineone.net/~mwarhurst/mechanisms.html