4.5 Endocrine disruptors
Then he was a she…
(Lou Reed, American rock singer)
In 1996, a book called Our Stolen Future was published, bringing to public attention a debate that had been simmering among biologists for some time. Written by Theo Colborn and two colleagues at the World Wildlife Fund (WWF), this book presented the hypothesis that certain industrial chemicals, commonly found as environmental pollutants, are threatening human health by disrupting the body's hormonal system. These chemicals, variously called endocrine disruptors (end-oh-krin), hormone mimics or, in the media, ‘gender benders’, could be playing a role in a range of problems, from reproductive and developmental abnormalities, to defects of the nervous system, to cancer. This disturbing hypothesis was based on studies of both wild and laboratory animals, for which there was a steady accumulation of evidence that certain xenobiotic chemicals were disrupting normal development and reproduction. One of the most common examples of endocrine disruption involves, to varying extents, the feminisation of males. There seem to be no endocrine disruptors that masculinise females, but several disrupt the normal functioning of the female reproductive system (US Environmental Protection Agency, 1997).
While it is now widely accepted that endocrine disruptors are having serious effects on a variety of wild animals, there is considerable debate among biologists as to whether human health and reproduction are being affected. If they are, it represents a possible cost of living in the modern ‘human zoo’.
Endocrine disruptors get their name because they interact with the endocrine (hormonal) system in the body. The endocrine system consists primarily of a number of endocrine glands (also known as ductless glands) that each secrete one or more hormones directly into the bloodstream. A hormone is a substance produced by an endocrine gland that is carried by the bloodstream to other organs or tissues where it acts to alter their structure or function.
An important effect of some hormones is to regulate behaviour. This is true of the ‘flight or fight’ hormone epinephrine (formerly known as adrenalin) which, secreted by the suprarenal glands in response to danger and other alarming stimuli, activates the body and facilitates a rapid response. It is less true of sex hormones, such as oestrogen or testosterone, which have little immediate effect on behaviour, but which have a profound, long-term, organising effect on the body. Thus, the level of testosterone determines the timing of adolescence in boys, for example. This organising effect is important in the context of endocrine disruption because it means that, if an organism's endocrine system is disrupted early in life, it can have profound consequences that can affect it throughout its life.
Fundamental to understanding how hormones and endocrine disruptors work is the concept of a receptor. A receptor is a large, specialised molecular structure embedded in the membrane that forms the outer layer of a cell (Figure 13). It consists primarily of proteins that have affinity for a specific hormone, drug or other natural or synthetic chemical. For example, cells in the mammary glands of mammals have receptors on their surface with a special affinity for the hormone oestrogen, which is secreted primarily by the ovaries. When oestrogen comes into contact with an oestrogen receptor on a cell, it initiates a change within that cell. By this mechanism, oestrogen controls mammary development at adolescence and function during reproduction. Mammary glands are said to be ‘target organs’ of oestrogen. This ‘special affinity’ involves a process called binding, in which a specific part of a hormone molecule becomes attached to part of the corresponding receptor on the surface of the target cell, triggering a change within the target cell. Because of the specificity of this relationship, the process of binding is often likened to a key being inserted into a lock (Figure 13).
Endocrine disruptors work because, although they are not hormones and often bear no obvious similarity to hormones, they happen to have in their molecular structure features that mimic the ‘key’ section of specific hormone molecules. Thus a substance that is not a hormone has the ability to ‘unlock the lock’ on target organs and thus behave as if the relevant hormone had become bound to them.
Before going on to examine endocrine disruptors in more detail, it is important to mention a related issue, the presence in the environment of real hormones. Women taking the contraceptive pill excrete substantial amounts of modified versions of human reproductive hormones, such as oestrogen, in their urine. Artificial hormones are not broken down in sewage treatment plants and so appear, sometimes in quite high concentrations, in sewage outflows into rivers. At a number of sites in the UK, male fish have been found to be feminised close to sewage outflows (Tyler et al., 1998).
It is important to emphasise that animals are very sensitive to very small variations in reproductive hormones. This is illustrated by work carried out by an American biologist, Fred vom Saal, who works on rodents (vom Saal and Bronson, 1978, vom Saal et al., 1999). Rodents have large litters and, during their development within their mother, embryos are lined up in the uterus in a row. In this row a male embryo may find itself between another two males, between two females, or between one of each. Vom Saal developed techniques to determine the exact position of each embryo prior to birth and to detect small variations in the behaviour of the young rodents that those embryos became as they grew up. He found that the behaviour of individuals was affected by their position in the uterus, as measured by variations in aggressive and sexual behaviour. Male rodents that had been between another two males in the uterus are more aggressive and sexually active than those that had been between two females. This effect is due to the fact that, even as embryos, young mammals secrete tiny quantities of sex hormones. This example gives credence to the hypothesis that very small amounts of hormone, or of hormone mimics, can influence animals as they develop.