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The Complexity of the Body
This page gives a very brief introduction to the endocrine, immune and nervous systems, and the important role of development.
This page focuses mainly on interactions between the endocrine system and the immune and nervous systems, including some recent references. If you want to know more I would recommend looking at recent text books covering each of the three systems and development. Knowledge of these systems is advancing rapidly, so the newer the text book, the better.
The hormonal or endocrine system
This system is the main subject of this web site, particularly the reproductive hormones. Hormones generally carry fairly long-lasting messages, in contrast to the rapid signalling of the nervous system. In 1997 more complexity was added to the attempts to understand the endocrine system, and potential effects of chemicals on it, when it was discovered that the 'female' hormone oestradiol is essential for male fertility (Sharpe, 1997). If this wasn't enough, it is now clear that there is not just one oestradiol receptor; there are several, and they all behave slightly differently, with differing levels in different tissues (Petersen et al., 1998).
The immune system
The immune system is responsible for resisting infectious agents, environmental substances and foreign or damaged cells (Dean and Murray, 1991). The capacity for immune response is determined early in development, so damage early in life will persist (Colborn, 1996). The immune and endocrine systems are linked by a variety of signalling systems, and much research on wild animals has demonstrated that endocrine disrupting chemicals can reduce the effectiveness of the immune system (Kavlock et al., 1996). A lot of this research has focused on marine animals and birds; for example, high levels of PCBs and DDT in the blood of dolphins was associated with decreased immune function and increased incidence of infection (Kavlock et al., 1996).
The nervous system
The function of the nervous system is the rapid communication of signals between different parts of the body, and the processing of these signals. The most complex part of the nervous system is the brain, where most of the processing occurs. Although most of the nervous system is protected from potential toxicants by the blood-brain barrier, some chemicals can penetrate this barrier (Anthony and Graham, 1991). In addition, this barrier is not fully developed until after birth, which is why the developing foetus is so sensitive to chemicals such as alcohol.
A US EPA workshop concluded that a variety of endocrine disrupting chemicals, including some PCBs, dioxins, DDT and chlorinated pesticides, are capably of producing neurotoxicity (Kavlock et al., 1996). Effects reported in the literature included changes in behaviour, learning and memory attention. 'Our Stolen Future' (Colborn et al., 1996) describes several of these studies. Most of these toxic effects are believed to occur due to the endocrine disrupting chemicals influencing the development of the nervous system.
The rest of the body
Other parts of the body are also affected by hormones. For example, blood vessels are influenced by oestrogen levels, with oestrogen exposure leading to relaxation of the walls of the vessels. Ruehlmann et al (1998) have found that 4-octyl phenol, p-nonylphenol and o,p'-DDT have the same effect as oestrogen.
Develoment
The timing of administration of a hormone disrupting chemical is particularly important for foetuses and young children, as the body's systems are most sensitive when they are under construction (Manson and Wise, 1991). During this period different events are occurring on different days, so providing small windows of time when the developing organism is extremely sensitive to hormone disrupting chemicals, for example during the formation of the testes (see the health page). Diethylstilbestrol (DES), a synthetic oestrogen, was taken by more than 5 million pregnant women between the late 1840s and the early 1970s, and led to many reproductive abnormalities in both male and female offspring (Toppari et al., 1996). Experiments on rats have since demonstrated how DES exposure at particular stages of foetal development leads to reproductive system damage, similar to that exhibited by the human victims (Toppari et al., 1996).
It is known that the developing foetus is the most sensitive stage in human development of organs such as the testes). The effects of many of these chemicals are additive; there is more debate about the extent of more than additive effects (see issues page), so exposure to a range of chemicals at a low levels has the same effect as exposure to one chemical at a higher level.
Crucial windows of sensitivity in male development
The development of the testis occurs almost entirely during early development in the womb. It is in this period that the Sertoli cells differentiate, and any exposure to oestrogen at this time reduces the number of Sertoli cells produced (Jensen et al., 1995). The Sertoli cells are responsible for producing sperm in later life, and it has been shown that the number of Sertoli cells is directly related to the sperm count, so fewer cells will lead to a lower sperm count (Jensen et al., 1995). It is also believed that abnormal germ cells, formed in early development, are responsible for most testicular cancers in later life (Jensen et al., 1995).
The oestrogen diethylstilbestrol (DES) was given to > 5 million pregnant mothers in the period between the late 1940s and the early 1970s to prevent miscarriage. Its use was stopped after a high incidence of a rare cervical cancer in pubertal girls exposed to DES in the uterus. It was later found that male offspring also had a higher level of reproductive abnormalities, including low sperm counts (Jensen et al., 1995). The case of DES is a clear indication that exposure of the foetus to external oestrogens can result in reproductive problems later in life (Toppari et al, 1996).
For the adult males, direct toxic effects on sperm production by chemicals such as phthalates could also be an issue. However as far as oestrogenic effects go, it is clear that the final 3 months of pregnancy and the first few months of life will be where any exposure of a male to oestrogens is likely to have the greatest effect. The research showing that metabolites of DDT can block the male hormonal system is worrying.