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Fundamental facts about environmental hormones: text of speech by Dr Susan Jobling at the BA Festival of Science 2004
September 07, 2004Fundamental facts about environmental hormones
Cancer may not be the only long-term health threat that we (and the other animals we share our planet with) face. Some researchers have suggested that minute amounts of certain environmental pollutants may adversely change the way wildlife (and possibly also humans) develop and reproduce. Researchers have been investigating these "environmental hormones" for several years and media coverage has highlighted concerns about the potential impacts of these so called environmental hormones on wildlife and on the human population. The scientific community is deeply divided about the questions being raised by the research findings. As with most new and complex fields, the issues surrounding environmental hormones are rife with debate, inconsistencies and controversy.
This presentation will provide an introduction to what environmental hormones are, what we know about what they do, what is not known and what is being done. It hopes to illustrate that the answers to these questions, and other mysteries surrounding environmental hormones, can only be provided by conducting both fundamental and applied scientific research. Unlike applied research, fundamental research may not always be of obvious benefit to society, but it may become so as the results of this research are utilised in more applied studies and there may be a gap spanning several years between the fundamental research result and its utilisation.
What are environmental hormones?
The term environmental hormone is commonly used to describe environmental agents that can alter the endocrine system of humans and wildlife. Fundamental research has taught us that the endocrine system is made up of specialised cells and glands under the control of a network of chemical signals or hormones. This communication network responds to stimuli by releasing hormones, the chemical messengers that carry instructions about essential bodily functions to target "receiver" cells throughout the body. The instructions are read by receptors within or on the surface of the "receiver" cell. Some hormonal instructions cause short term temporary changes, such as a faster heart beat. Others dictate more long-term development, such as initiation of the menstrual cycle or even bone or muscle growth, or development of the reproductive organs (ovaries and testes) in the developing foetus.
Our laboratory, like other laboratories working in this emerging field of environmental endocrine research have looked at chemical pollutants that mimic or block the action of natural hormones and hence fool the body into thinking that they are hormones or anti-hormones. Communication is the one essential property of life and hence chemicals that alter this information flow can have consequences that may be deleterious to individuals and/or populations. Environmental chemicals known to do this do so most often by interacting with receptors in a family called the steroid family, particularly the oestrogen and androgen receptors. They include ubiquitous and persistent pesticides, plasticizers, pharmaceuticals and natural hormones, many of which end up down our drains and in our rivers in which fish and other aquatic organisms reside. In recent years, the increased interest in these contaminants has led to an increasing amount of studies on the levels of drugs in wastewater. An early study in 1977 reported that 8.5kg/day of a metabolite of aspirin was found in waste water in Kansas City in the USA. This prompted speculation that "with millions of women taking oral contraceptives, some environmental contamination with estrogenic chemicals is a distinct possibility". More than 20 years later a component of the contraceptive pill 17a-ethinylestradiol was found in trace amounts in waste water in the U.K. and it is only now that we are beginning to understand the biological significance of the presence of this hormone in rivers. Whilst many environmental hormones are weakly active compared with natural hormones, ethynylestradiol may be many times potent than the hormones which our bodies produce. In order to understand its effects, let us consider what fundamental research has taught us about how oestrogen acts:
How do hormones and environmental hormones act?
Estrogens control the female reproductive cycle and the development of the female (and male) reproductive organs. They also influence bone density, can stimulate the growth of some breast tumours. Fundamental research into hormone action led to the discovery that small amounts of the hormone oestrogen given early in development could cause acute feminisation of the male in animals from fish through to humans. In fish, oestrogen exposure during early life can cause the development of intersex (with both male and female reproductive organs) in adult fish and hence, when these types of fish were found in UK rivers downstream from sewage treatment works, oestrogen was suspected to be contaminating our waters. Further research of a more applied nature has shown that this is indeed the case and has also led to the discovery that many other chemicals (apart from natural hormones contraceptive pill hormones), which were previously thought to be harmless, possess hormonal or anti-hormonal activity. Included in this list of chemicals are breakdown products of detergents, and plasticizers, all of which are commonly used industrial chemicals.
Intersex fish are less fertile than normal fish and a recent survey of UK Rivers by the Environment Agency and Brunel and Exeter Universities has shown that this phenomenon is extremely widespread, affecting fish at over 40 sites around the UK. This is a clear example of how fundamental research has helped to explain abnormalities found in wildlife populations. Moreover, recognition of these patterns of disruption in fish populations and its association with contamination of rivers by particular environmental hormones at particular concentrations is also enabling us to anticipate where we might be expected to see the effects of environmental hormones. If we can predict, then theoretically, we should also be able to prevent and hence, areas where the effects of environmental hormones are expected to cause problems for fish could be targeted for remediation.
The research on fish suggests that very low concentrations of environmental hormones can affect reproductive form and (in extreme cases) function in fish. The research also suggests that intersex could be a progressive condition that worsens with age. Could the same be true of humans and so could minute amounts of these environmental hormones that we are exposed to daily affect human health in the long term? The answer to this question remains elusive although patterns of reproductive and developmental disruption that could be caused by environmental hormones are present in the human population. These patterns have been discerned through fundamental research on the actions of hormones and this is why more fundamental research is necessary to further our understanding of hormone action.
Researchers are also researching at what threshold amounts and during what stages of development, chemicals can produce harmful effects via effects on the endocrine system. Toxicology teaches us that the dose of a pollutant or stressor makes the poison and hence the more of a chemical you are exposed to the more likely you are to be poisoned.essentially, when we find a poisonous dose of a chemical, we assume that all doses below this dose are safe. Fundamental research on hormones has, however, taught us that, unlike toxicants, hormones (and therefore possibly also environmental hormones) act by feedback loops so a little hormone may stimulate a target organ and induce a response (which might be adverse or beneficial). Conversely, a lot of hormone may trigger the endocrine system to send a message to the target organ telling it to switch off the response (which might also be adverse or beneficial). This is the way in which the body regulates the production of its own hormones. The problem with environmental hormones is that the body cannot control when it is exposed to these molecules and hence it may be forced to receive these signals at the wrong time. If this happens, it could lead to hormonal imbalances.
The low dose issue (as it has become known) is one of the most controversial areas of the environmental hormone field. It has revealed some very unexpected findings. Perhaps the most important of these is that a hormonally active chemical called bisphenol-A, produced in enormous quantities by the chemical industry, can cause sexual disruption in the tropical snail called Marisa cornuarietis at very low environmentally relevant, concentrations. The effects include a massive stimulation of egg production by the female snails, leading (in some cases) to rupture of the oviducts and death. These findings were reported by a German ecotoxicology laboratory researching suitable methods and test organisms for investigating environmental hormones. They have sparked huge controversy. The controversy was mainly because bisphenol-A had hitherto been shown to have only weak hormonal activity in the animals in which it had been tested. Conversely, these studies suggested that the chemical was exquisitely potent, at least to snails. Further studies by the same investigators and in our laboratories have shown that reproduction in some snails is also sensitive hormones, such as ethynyloestradiol, the contraceptive pill hormone. These results are also interesting from a fundamental scientific point of view as prior to these publications, although the signalling molecule oestradiol was known to be present in many invertebrates from corals on the reef to starfish, the signalling recognition system, or oestrogen receptor, had not been found in any of the invertebrates and in fact was thought to have arisen with the evolution of the vertebrates.
What happened next provides us with an example of how applied toxicological research can spark new areas of fundamental research. Following this publication, many laboratories (including our own) began the search for oestrogen receptors in snails in an effort to understand how chemicals such as bisphenol-A can cause effects in these animals. As a result of this research, the Japanese discovered the first oestrogen-receptor like molecule in a marine snail and the Americans discovered a similar molecule in a sea slug. In our own laboratory, we have discovered that Marisa cornuarietis, the snail in the original study in which BPA was shown to be so potent, also has an oestrogen receptor. These findings suggest that oestrogen was the first hormone to evolve and that the oestrogen signalling system must date back more than 600 million years rather than only 400 million years as was previously thought. Studies are now underway to try to understand how this receptor works in the snail as the information published to date suggests that the receptor is not regulated by oestrogen, at least in the sea slug, suggesting that this receptor may have lost its function here. If this is also correct in snails, then what is the explanation for the profound effects that estrogens have in Marisa? It is possible that estrogens act via non-receptor mediated mechanisms as these mechanisms have been documented to exist in higher organisms. Further research by our research group will hopefully provide the answers to these (and other) questions.
Remaining questions:
To further understand how environmental hormones work and if they threaten wildlife and human health, there are several additional questions that need to be asked and answered:
1.Can wildlife data be applied to humans when it is clear that some compounds have different effects in different kinds of animals?
2.Can laboratory tests on cells explain and predict effects in living organisms, especially since chemicals can affect more than one organ?
3.How do mixtures react and interact with the endocrine system and with one another?
4.How many more chemicals are likely to act like hormones?
5.What levels of exposure over what time frames cause adverse effects?
6.Does exposure to environmental hormones pose a greater threat to developing embryos than to adults and thus impact future generations?
7.How do variables such as profession, age, and genetics etc influence susceptibility and does exposure to one chemical predispose or sensitize an animal to a subsequent exposure?
8.How important are environmental hormones compared with other major issues affecting human and wildlife health?
What is being done?
People who are concerned about health usually want answers today, rather than tomorrow. The issue of environmental hormones, however, involves complex biological systems and diverse health responses and hence, cause and effect data are hard to find. Getting ahead of science could lead to wrong or misleading answers, although the lack of answers is frustrating for policy makers who are pressurised to act now and ask questions later. Notwithstanding this, even without hard evidence, the potential health threat and social and economic risks posed by the environmental hormone issue has forced governments and the public to take notice. We are now relying on scientific, political and public debate to weigh the evidence for and against the endocrine disruptor hypothesis and decide how to deal with it. Governments around the world are gathering information, funding research and developing screening and testing programmes and setting up new policies. Individuals are becoming informed through the media attention that this issue has received. The endocrine disruption/environmental hormone hypothesis deserves full investigation and this will require quite significant research, both fundamental and applied for the foreseeable future.
Brunel University
What are environmental hormones?
The term environmental hormone is commonly used to describe environmental agents that can alter the endocrine system of humans and wildlife. Fundamental research has taught us that the endocrine system is made up of specialised cells and glands under the control of a network of chemical signals or hormones. This communication network responds to stimuli by releasing hormones, the chemical messengers that carry instructions about essential bodily functions to target "receiver" cells throughout the body. The instructions are read by receptors within or on the surface of the "receiver" cell. Some hormonal instructions cause short term temporary changes, such as a faster heart beat. Others dictate more long-term development, such as initiation of the menstrual cycle or even bone or muscle growth, or development of the reproductive organs (ovaries and testes) in the developing foetus.
Our laboratory, like other laboratories working in this emerging field of environmental endocrine research have looked at chemical pollutants that mimic or block the action of natural hormones and hence fool the body into thinking that they are hormones or anti-hormones. Communication is the one essential property of life and hence chemicals that alter this information flow can have consequences that may be deleterious to individuals and/or populations. Environmental chemicals known to do this do so most often by interacting with receptors in a family called the steroid family, particularly the oestrogen and androgen receptors. They include ubiquitous and persistent pesticides, plasticizers, pharmaceuticals and natural hormones, many of which end up down our drains and in our rivers in which fish and other aquatic organisms reside. In recent years, the increased interest in these contaminants has led to an increasing amount of studies on the levels of drugs in wastewater. An early study in 1977 reported that 8.5kg/day of a metabolite of aspirin was found in waste water in Kansas City in the USA. This prompted speculation that "with millions of women taking oral contraceptives, some environmental contamination with estrogenic chemicals is a distinct possibility". More than 20 years later a component of the contraceptive pill 17a-ethinylestradiol was found in trace amounts in waste water in the U.K. and it is only now that we are beginning to understand the biological significance of the presence of this hormone in rivers. Whilst many environmental hormones are weakly active compared with natural hormones, ethynylestradiol may be many times potent than the hormones which our bodies produce. In order to understand its effects, let us consider what fundamental research has taught us about how oestrogen acts:
How do hormones and environmental hormones act?
Estrogens control the female reproductive cycle and the development of the female (and male) reproductive organs. They also influence bone density, can stimulate the growth of some breast tumours. Fundamental research into hormone action led to the discovery that small amounts of the hormone oestrogen given early in development could cause acute feminisation of the male in animals from fish through to humans. In fish, oestrogen exposure during early life can cause the development of intersex (with both male and female reproductive organs) in adult fish and hence, when these types of fish were found in UK rivers downstream from sewage treatment works, oestrogen was suspected to be contaminating our waters. Further research of a more applied nature has shown that this is indeed the case and has also led to the discovery that many other chemicals (apart from natural hormones contraceptive pill hormones), which were previously thought to be harmless, possess hormonal or anti-hormonal activity. Included in this list of chemicals are breakdown products of detergents, and plasticizers, all of which are commonly used industrial chemicals.
Intersex fish are less fertile than normal fish and a recent survey of UK Rivers by the Environment Agency and Brunel and Exeter Universities has shown that this phenomenon is extremely widespread, affecting fish at over 40 sites around the UK. This is a clear example of how fundamental research has helped to explain abnormalities found in wildlife populations. Moreover, recognition of these patterns of disruption in fish populations and its association with contamination of rivers by particular environmental hormones at particular concentrations is also enabling us to anticipate where we might be expected to see the effects of environmental hormones. If we can predict, then theoretically, we should also be able to prevent and hence, areas where the effects of environmental hormones are expected to cause problems for fish could be targeted for remediation.
The research on fish suggests that very low concentrations of environmental hormones can affect reproductive form and (in extreme cases) function in fish. The research also suggests that intersex could be a progressive condition that worsens with age. Could the same be true of humans and so could minute amounts of these environmental hormones that we are exposed to daily affect human health in the long term? The answer to this question remains elusive although patterns of reproductive and developmental disruption that could be caused by environmental hormones are present in the human population. These patterns have been discerned through fundamental research on the actions of hormones and this is why more fundamental research is necessary to further our understanding of hormone action.
Researchers are also researching at what threshold amounts and during what stages of development, chemicals can produce harmful effects via effects on the endocrine system. Toxicology teaches us that the dose of a pollutant or stressor makes the poison and hence the more of a chemical you are exposed to the more likely you are to be poisoned.essentially, when we find a poisonous dose of a chemical, we assume that all doses below this dose are safe. Fundamental research on hormones has, however, taught us that, unlike toxicants, hormones (and therefore possibly also environmental hormones) act by feedback loops so a little hormone may stimulate a target organ and induce a response (which might be adverse or beneficial). Conversely, a lot of hormone may trigger the endocrine system to send a message to the target organ telling it to switch off the response (which might also be adverse or beneficial). This is the way in which the body regulates the production of its own hormones. The problem with environmental hormones is that the body cannot control when it is exposed to these molecules and hence it may be forced to receive these signals at the wrong time. If this happens, it could lead to hormonal imbalances.
The low dose issue (as it has become known) is one of the most controversial areas of the environmental hormone field. It has revealed some very unexpected findings. Perhaps the most important of these is that a hormonally active chemical called bisphenol-A, produced in enormous quantities by the chemical industry, can cause sexual disruption in the tropical snail called Marisa cornuarietis at very low environmentally relevant, concentrations. The effects include a massive stimulation of egg production by the female snails, leading (in some cases) to rupture of the oviducts and death. These findings were reported by a German ecotoxicology laboratory researching suitable methods and test organisms for investigating environmental hormones. They have sparked huge controversy. The controversy was mainly because bisphenol-A had hitherto been shown to have only weak hormonal activity in the animals in which it had been tested. Conversely, these studies suggested that the chemical was exquisitely potent, at least to snails. Further studies by the same investigators and in our laboratories have shown that reproduction in some snails is also sensitive hormones, such as ethynyloestradiol, the contraceptive pill hormone. These results are also interesting from a fundamental scientific point of view as prior to these publications, although the signalling molecule oestradiol was known to be present in many invertebrates from corals on the reef to starfish, the signalling recognition system, or oestrogen receptor, had not been found in any of the invertebrates and in fact was thought to have arisen with the evolution of the vertebrates.
What happened next provides us with an example of how applied toxicological research can spark new areas of fundamental research. Following this publication, many laboratories (including our own) began the search for oestrogen receptors in snails in an effort to understand how chemicals such as bisphenol-A can cause effects in these animals. As a result of this research, the Japanese discovered the first oestrogen-receptor like molecule in a marine snail and the Americans discovered a similar molecule in a sea slug. In our own laboratory, we have discovered that Marisa cornuarietis, the snail in the original study in which BPA was shown to be so potent, also has an oestrogen receptor. These findings suggest that oestrogen was the first hormone to evolve and that the oestrogen signalling system must date back more than 600 million years rather than only 400 million years as was previously thought. Studies are now underway to try to understand how this receptor works in the snail as the information published to date suggests that the receptor is not regulated by oestrogen, at least in the sea slug, suggesting that this receptor may have lost its function here. If this is also correct in snails, then what is the explanation for the profound effects that estrogens have in Marisa? It is possible that estrogens act via non-receptor mediated mechanisms as these mechanisms have been documented to exist in higher organisms. Further research by our research group will hopefully provide the answers to these (and other) questions.
Remaining questions:
To further understand how environmental hormones work and if they threaten wildlife and human health, there are several additional questions that need to be asked and answered:
1.Can wildlife data be applied to humans when it is clear that some compounds have different effects in different kinds of animals?
2.Can laboratory tests on cells explain and predict effects in living organisms, especially since chemicals can affect more than one organ?
3.How do mixtures react and interact with the endocrine system and with one another?
4.How many more chemicals are likely to act like hormones?
5.What levels of exposure over what time frames cause adverse effects?
6.Does exposure to environmental hormones pose a greater threat to developing embryos than to adults and thus impact future generations?
7.How do variables such as profession, age, and genetics etc influence susceptibility and does exposure to one chemical predispose or sensitize an animal to a subsequent exposure?
8.How important are environmental hormones compared with other major issues affecting human and wildlife health?
What is being done?
People who are concerned about health usually want answers today, rather than tomorrow. The issue of environmental hormones, however, involves complex biological systems and diverse health responses and hence, cause and effect data are hard to find. Getting ahead of science could lead to wrong or misleading answers, although the lack of answers is frustrating for policy makers who are pressurised to act now and ask questions later. Notwithstanding this, even without hard evidence, the potential health threat and social and economic risks posed by the environmental hormone issue has forced governments and the public to take notice. We are now relying on scientific, political and public debate to weigh the evidence for and against the endocrine disruptor hypothesis and decide how to deal with it. Governments around the world are gathering information, funding research and developing screening and testing programmes and setting up new policies. Individuals are becoming informed through the media attention that this issue has received. The endocrine disruption/environmental hormone hypothesis deserves full investigation and this will require quite significant research, both fundamental and applied for the foreseeable future.
Brunel University
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