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Major international hormone conference
November 14, 2000MAJOR INTERNATIONAL HORMONE CONFERENCE
LONDON 20 – 21 NOVEMBER 2000
Over 500 leading UK and international hormone specialists will meet at the Royal College of Physicians in London over the next two days to attend the annual meeting of the Society for Endocrinology. This major annual meeting provides a forum to present the latest hormone research. The 2000 meeting includes talks from some of the world’s leading hormone researchers and clinicians, as well as groundbreaking research by up and coming endocrinologists.
Amongst the new research being presented over the two days is:
1. The actions of ecstasy on water regulating hormones – how much should you drink, and why young women are at greater risk.
There have been several high-profile deaths caused by excess water consumption after taking MDMA (ecstasy). MDMA stimulates the release of the water regulating hormone vasopressin, which could contribute to the hyponatraemia (excess water retention) which has been associated with deaths from the use of this drug.
Ground breaking research by Professor Mary Forsling and her colleagues (Guy’s Hospital Campus, and the Drug Control Centre and Department of Pharmacy, King’s College, London) has led them to propose a new theory that it is not the action of ecstasy itself which causes these problems, but one of the products from its metabolism by the body. Professor Forsling says, “Each person could react differently to this drug. Depending on factors such as metabolism, the body’s absorption rate, the quantity of water consumed, and various other variables, this could mean a potentially different level of toxicity in each person”.
This metabolite (HMMA) of ecstasy stimulates the release of the hormone vasopressin, which encourages the body to retain water. If the water in the body reaches a critical high level, the salt/water balance is disturbed – resulting in a dangerously low level of sodium in the body. Professor Forsling goes on to explain that women of reproductive age cannot tolerate these low levels of sodium in their bodies in the same way that younger males and older adults can. This often has serious consequences and potentially can result in death. She says, “If your body breaks down this drug in a particular way, the consequences could be potentially fatal”.
2. Hormone predicts premature delivery of babies
In 1995 Professor Roger Smith (Mothers & Babies Research Centre, NSW, Australia) and his team discovered the existence of a type of ‘biological clock’ in the placenta which determines the length of human pregnancy. They found that measuring corticotrophin releasing hormone (CRH), a hormone found in the placenta, indicates the timing of the end of pregnancy – early, on time or late.
Currently, pre-term birth occurs in 6-15 % of births worldwide. Many pre-term babies die in the immediate period after birth, and amongst those who survive there is an increased risk of intellectual handicaps and learning difficulties, as well as cerebral palsy, blindness and deafness.
Recently the team has been working on methods to give more accurate predictions by investigating the molecular mechanisms of the ‘clock’ in the placenta in a wide number of species. Professor Smith says, “We have found that the stress hormone cortisol plays a key role in the workings of the placental clock”. The group has also looked at other ways of monitoring the activity of the clock to improve its accuracy. This work, which will be discussed at today’s meeting, may lead to new effective ways of treating women at high risk of pre-term labour and eventually into methods of treating and preventing the problem.
3. New understanding of female hormones may revolutionise future HRT for women
Recent new work on the action of oestrogen has led to a dramatic shift in our understanding of this hormone’s function and may revolutionise HRT of postmenopausal women and thereby have an immense impact on women’s health in the future.
The first oestrogen receptor was discovered by Dr. Elwood Jensen in 1958. In 1995, Professor Jan-Ćke Gustafsson and his team at the Huddinge University Hospital, Karolinska Institute, Sweden, discovered another receptor: oestrogen receptor beta (ERb). At the time this was a quite sensational finding since, as until then, only one oestrogen receptor (now called ERa) was known to exist.
ERb appears to be very widespread in the body and is found in large concentrations particularly in the prostate, ovary, brain, lung, large intestine, testis, mammary gland, bone and the cardiovascular system, as well as the immune system. One important function of ERb appears to be to “control” or balance ERa by reducing its activity.
Professor Gustafsson says, “This is particularly important in the context of oestrogen associated cancer where ERa appears to be the “bad” guy which emits proliferating signals whereas ERb seems to be the “good” guy which produces antiproliferative signals. This means that ERb specific drugs could be extremely valuable for HRT (hormone replacement therapy) since they might give the desired effects (protecting against osteoporosis, depression and Alzheimer’s disease, cardiovascular and prostrate disease) but not the undesired ones (mammary and endometrial cancer)”.
Professor Gustafsson will also discuss new research on the role of ERb in the development of the brain and present results that provide evidence that oestrogens are also important in the maintenance of the central nervous system. He will outline the impact that this may have on the future role of HRT in preventing Alzheimer’s disease.
4. Targeted radiotherapy hits endocrine cancers
Carcinoid syndrome is a rare, difficult to treat cancer. The cancerous cells produce hormones, which can lead to diarrhoea and flushing. Because of this, the patients are often misdiagnosed, or labelled as hypochondriacs.
Now a multidisciplinary team at St Bartholomew’s Hospital has found a way of specifically homing in on and controlling these tumours. A chemical called mIBG attaches itself to around 40% of these tumours. Attaching radioactive iodine to the mIBG molecule means the radioisotope can specifically attack the tumour cells. Results show almost a doubling in survival rate over established methods. In the future it is hoped that similar work with an even more promising radiolabelled hormone called octreotide, which attaches to almost 80% of carcinoid tumour cells, may be useful for treating many more of such tumours.
Professor Grossman says, “ This is one of the first practical targeted cancer therapies, but has rarely been systematically used for these tumours in the past. Our results show that, for carcinoid tumours, this treatment is more effective than chemotherapy. The application of this new treatment will be limited only by cost”.
5. New gene ‘switch’ to reduce weight gain through a change in metabolism
The part of the brain which controls feeding and weight – the hypothalamus - produces a hormone neuropeptide Y, whose levels rise in situations associated with increased appetite e.g. fasting, exercise and lactation.
Dr Wing May Kong and the team of Professor S. R Bloom at the ICSM Endocrine Unit at the Hammersmith Hospital, have used an innovative new gene therapy technique to increase the levels of the neuropeptide Y in the hypothalamus in rats. This results directly in obesity through increased feeding and a reduced metabolism.
The team has now used a similar technique to ‘switch off’ the neuropeptide Y gene in the hypothalamus which has resulted in reduced weight gain and with no reduction in feeding, suggesting the reduced weight gain is due to increased metabolism.
Dr Kong says, “Our results demonstrate that switching off this gene reduces weight gain through an increase in metabolism rather than a reduction in food intake”. This work could lead to anti-obesity treatments targeting the neuropeptide Y system which work by increasing metabolism. This may be useful for some obese patients. However, many clinicians may consider a drug that increases metabolism less desirable than one that reduces appetite.
6. Lock and key combination therapy targets head and neck cancers
Many cancer cells have EGF (Epidermal Growth Factor) receptors on their surface. Dr John Mendelsohn’s group (The University of Texas M. D. Anderson Cancer Centre, Houston, Texas) hypothesised that blocking these receptors with a highly specific molecule (a monoclonal antibody) would block the growth of the cancers. They developed a monoclonal antibody called C225, which specifically fits the EGF receptor like a key does a lock. They found that C225 did indeed slow down cancer cell growth, both in the cultured cells and in animals. It’s believed that blocking the EGF receptor inhibits cancer cell proliferation and stops cancer cells from forming the blood supply network they need to support continued growth.
Dr Mendelsohn’s group is now using anticancer drugs or radiation in combination with the C225 antibody. This combination therapy is proving extremely successful in combating head and neck tumours. Dr Mendelsohn says “This is an exciting area of cancer research, with much interest being shown in these methods. The preliminary results are very promising, and we are now testing the therapy in Phase II and Phase III clinical trials. We believe we are getting quite close to producing a working therapy against these and other epithelial tumours”.
7. New theory on growth hormone action in embryos could assist IVF
Contrary to current accepted theories on the timing of action of infant growth hormone, Professor Peter Kaye and his team from the University of Queensland, Australia, have found that growth hormone acts to stimulate growth of the pre-implantation embryo, rather than being involved only in postnatal growth.
They have shown that growth hormone affects embryos directly rather than, as previously thought, through a secondary hormone (insulin like growth factor 1). They have also found that another closely related hormone, prolactin, is produced by embryos which also acts to stimulate the embryo. This research implicates two hormones, growth hormone and prolactin, in early embryonic development where previously they were regarded to be involved in postnatal growth and function.
Professor Kaye says, “This could influence assisted reproduction in the future, as the addition of these two hormones to IVF culture systems may improve development of embryos and thus pregnancy. Our results also show that the developing embryo is subject to much more complex regulatory systems than previously thought; it may be that a failure of these systems contributes towards infertility”.
8. Genetic discoveries may open door to understanding of Type 2 diabetes and Syndrome X
Insulin resistance - where people actually produce insulin, but their cells don’t respond to it - is becoming one of the diseases of the millennium. Almost all type 2 (what used to be called adult onset) diabetics have insulin resistance. Type 2 diabetes affects up to 2 million Britons. Insulin resistance is not only associated with diabetes, but may be the key to the understanding of Syndrome X, where insulin-resistant patients also have obesity, hyperlipidemia, and high blood pressure. These patients are amongst the prime candidates for heart and circulation diseases.
Professor Stephen O’Rahilly (University of Cambridge) and his colleagues have identified 200 patients with severe insulin resistance. They have been genetically screening them, and have identified a new genetic mutation, which seems to lead directly to severe insulin resistance. This mutation, in the PPAR gamma hormone receptor, is especially significant because this receptor is the target for the new thiazolidinedione treatments, which reduce insulin resistance (these drugs are now coming onto the market in the UK). Identifying this mutation may be the beginning of understanding the mechanism of insulin resistance.
As part of the genetic screening work, Professor O’Rahilly’s group has also discovered that 5% of severely obese children have a mutation in another hormone receptor (the melanocortin 4 receptor). Discovery of this gene mutation has established it as the most common cause of human obesity detected to date. Again, these findings will help develop new drug targets to combat the current rapid increase in obesity in children.
9. Testosterone replacement: assessing its place in the men’s health revolution
Recent evidence suggests that androgens (including testosterone) may be protective in coronary heart disease in males. In this short symposium prominent British and American clinicians will present new data on the future potential of testosterone replacement and on the importance of androgens in coronary heart disease.
Amongst other presentations, Dr Hugh Jones (Barnsley District General Hospital) will present recent findings that demonstrate that men with coronary artery disease have lower testosterone levels than men with normal non-diseased coronary arteries. Dr Jones will also discuss the future potential of using testosterone as a treatment for common heart conditions such as angina.
There will be a high scientific content in all talks and any press attendance at the talks themselves will have to be cleared with the speakers, however you will be most welcome to attend the meeting to interview the speakers by prior arrangement. Please contact Tom Parkhill or Victoria Withy on
01454 201 612 or 07971 691 774, or via email: tom.parkhill@endocrinology.org or victoria.withy@endocrinology.org.
Please credit the Society for Endocrinology in any media coverage of this meeting.
We would be happy to provide you with general information about the Society if required.
Society for Endocrinology
1. The actions of ecstasy on water regulating hormones – how much should you drink, and why young women are at greater risk.
There have been several high-profile deaths caused by excess water consumption after taking MDMA (ecstasy). MDMA stimulates the release of the water regulating hormone vasopressin, which could contribute to the hyponatraemia (excess water retention) which has been associated with deaths from the use of this drug.
Ground breaking research by Professor Mary Forsling and her colleagues (Guy’s Hospital Campus, and the Drug Control Centre and Department of Pharmacy, King’s College, London) has led them to propose a new theory that it is not the action of ecstasy itself which causes these problems, but one of the products from its metabolism by the body. Professor Forsling says, “Each person could react differently to this drug. Depending on factors such as metabolism, the body’s absorption rate, the quantity of water consumed, and various other variables, this could mean a potentially different level of toxicity in each person”.
This metabolite (HMMA) of ecstasy stimulates the release of the hormone vasopressin, which encourages the body to retain water. If the water in the body reaches a critical high level, the salt/water balance is disturbed – resulting in a dangerously low level of sodium in the body. Professor Forsling goes on to explain that women of reproductive age cannot tolerate these low levels of sodium in their bodies in the same way that younger males and older adults can. This often has serious consequences and potentially can result in death. She says, “If your body breaks down this drug in a particular way, the consequences could be potentially fatal”.
2. Hormone predicts premature delivery of babies
In 1995 Professor Roger Smith (Mothers & Babies Research Centre, NSW, Australia) and his team discovered the existence of a type of ‘biological clock’ in the placenta which determines the length of human pregnancy. They found that measuring corticotrophin releasing hormone (CRH), a hormone found in the placenta, indicates the timing of the end of pregnancy – early, on time or late.
Currently, pre-term birth occurs in 6-15 % of births worldwide. Many pre-term babies die in the immediate period after birth, and amongst those who survive there is an increased risk of intellectual handicaps and learning difficulties, as well as cerebral palsy, blindness and deafness.
Recently the team has been working on methods to give more accurate predictions by investigating the molecular mechanisms of the ‘clock’ in the placenta in a wide number of species. Professor Smith says, “We have found that the stress hormone cortisol plays a key role in the workings of the placental clock”. The group has also looked at other ways of monitoring the activity of the clock to improve its accuracy. This work, which will be discussed at today’s meeting, may lead to new effective ways of treating women at high risk of pre-term labour and eventually into methods of treating and preventing the problem.
3. New understanding of female hormones may revolutionise future HRT for women
Recent new work on the action of oestrogen has led to a dramatic shift in our understanding of this hormone’s function and may revolutionise HRT of postmenopausal women and thereby have an immense impact on women’s health in the future.
The first oestrogen receptor was discovered by Dr. Elwood Jensen in 1958. In 1995, Professor Jan-Ćke Gustafsson and his team at the Huddinge University Hospital, Karolinska Institute, Sweden, discovered another receptor: oestrogen receptor beta (ERb). At the time this was a quite sensational finding since, as until then, only one oestrogen receptor (now called ERa) was known to exist.
ERb appears to be very widespread in the body and is found in large concentrations particularly in the prostate, ovary, brain, lung, large intestine, testis, mammary gland, bone and the cardiovascular system, as well as the immune system. One important function of ERb appears to be to “control” or balance ERa by reducing its activity.
Professor Gustafsson says, “This is particularly important in the context of oestrogen associated cancer where ERa appears to be the “bad” guy which emits proliferating signals whereas ERb seems to be the “good” guy which produces antiproliferative signals. This means that ERb specific drugs could be extremely valuable for HRT (hormone replacement therapy) since they might give the desired effects (protecting against osteoporosis, depression and Alzheimer’s disease, cardiovascular and prostrate disease) but not the undesired ones (mammary and endometrial cancer)”.
Professor Gustafsson will also discuss new research on the role of ERb in the development of the brain and present results that provide evidence that oestrogens are also important in the maintenance of the central nervous system. He will outline the impact that this may have on the future role of HRT in preventing Alzheimer’s disease.
4. Targeted radiotherapy hits endocrine cancers
Carcinoid syndrome is a rare, difficult to treat cancer. The cancerous cells produce hormones, which can lead to diarrhoea and flushing. Because of this, the patients are often misdiagnosed, or labelled as hypochondriacs.
Now a multidisciplinary team at St Bartholomew’s Hospital has found a way of specifically homing in on and controlling these tumours. A chemical called mIBG attaches itself to around 40% of these tumours. Attaching radioactive iodine to the mIBG molecule means the radioisotope can specifically attack the tumour cells. Results show almost a doubling in survival rate over established methods. In the future it is hoped that similar work with an even more promising radiolabelled hormone called octreotide, which attaches to almost 80% of carcinoid tumour cells, may be useful for treating many more of such tumours.
Professor Grossman says, “ This is one of the first practical targeted cancer therapies, but has rarely been systematically used for these tumours in the past. Our results show that, for carcinoid tumours, this treatment is more effective than chemotherapy. The application of this new treatment will be limited only by cost”.
5. New gene ‘switch’ to reduce weight gain through a change in metabolism
The part of the brain which controls feeding and weight – the hypothalamus - produces a hormone neuropeptide Y, whose levels rise in situations associated with increased appetite e.g. fasting, exercise and lactation.
Dr Wing May Kong and the team of Professor S. R Bloom at the ICSM Endocrine Unit at the Hammersmith Hospital, have used an innovative new gene therapy technique to increase the levels of the neuropeptide Y in the hypothalamus in rats. This results directly in obesity through increased feeding and a reduced metabolism.
The team has now used a similar technique to ‘switch off’ the neuropeptide Y gene in the hypothalamus which has resulted in reduced weight gain and with no reduction in feeding, suggesting the reduced weight gain is due to increased metabolism.
Dr Kong says, “Our results demonstrate that switching off this gene reduces weight gain through an increase in metabolism rather than a reduction in food intake”. This work could lead to anti-obesity treatments targeting the neuropeptide Y system which work by increasing metabolism. This may be useful for some obese patients. However, many clinicians may consider a drug that increases metabolism less desirable than one that reduces appetite.
6. Lock and key combination therapy targets head and neck cancers
Many cancer cells have EGF (Epidermal Growth Factor) receptors on their surface. Dr John Mendelsohn’s group (The University of Texas M. D. Anderson Cancer Centre, Houston, Texas) hypothesised that blocking these receptors with a highly specific molecule (a monoclonal antibody) would block the growth of the cancers. They developed a monoclonal antibody called C225, which specifically fits the EGF receptor like a key does a lock. They found that C225 did indeed slow down cancer cell growth, both in the cultured cells and in animals. It’s believed that blocking the EGF receptor inhibits cancer cell proliferation and stops cancer cells from forming the blood supply network they need to support continued growth.
Dr Mendelsohn’s group is now using anticancer drugs or radiation in combination with the C225 antibody. This combination therapy is proving extremely successful in combating head and neck tumours. Dr Mendelsohn says “This is an exciting area of cancer research, with much interest being shown in these methods. The preliminary results are very promising, and we are now testing the therapy in Phase II and Phase III clinical trials. We believe we are getting quite close to producing a working therapy against these and other epithelial tumours”.
7. New theory on growth hormone action in embryos could assist IVF
Contrary to current accepted theories on the timing of action of infant growth hormone, Professor Peter Kaye and his team from the University of Queensland, Australia, have found that growth hormone acts to stimulate growth of the pre-implantation embryo, rather than being involved only in postnatal growth.
They have shown that growth hormone affects embryos directly rather than, as previously thought, through a secondary hormone (insulin like growth factor 1). They have also found that another closely related hormone, prolactin, is produced by embryos which also acts to stimulate the embryo. This research implicates two hormones, growth hormone and prolactin, in early embryonic development where previously they were regarded to be involved in postnatal growth and function.
Professor Kaye says, “This could influence assisted reproduction in the future, as the addition of these two hormones to IVF culture systems may improve development of embryos and thus pregnancy. Our results also show that the developing embryo is subject to much more complex regulatory systems than previously thought; it may be that a failure of these systems contributes towards infertility”.
8. Genetic discoveries may open door to understanding of Type 2 diabetes and Syndrome X
Insulin resistance - where people actually produce insulin, but their cells don’t respond to it - is becoming one of the diseases of the millennium. Almost all type 2 (what used to be called adult onset) diabetics have insulin resistance. Type 2 diabetes affects up to 2 million Britons. Insulin resistance is not only associated with diabetes, but may be the key to the understanding of Syndrome X, where insulin-resistant patients also have obesity, hyperlipidemia, and high blood pressure. These patients are amongst the prime candidates for heart and circulation diseases.
Professor Stephen O’Rahilly (University of Cambridge) and his colleagues have identified 200 patients with severe insulin resistance. They have been genetically screening them, and have identified a new genetic mutation, which seems to lead directly to severe insulin resistance. This mutation, in the PPAR gamma hormone receptor, is especially significant because this receptor is the target for the new thiazolidinedione treatments, which reduce insulin resistance (these drugs are now coming onto the market in the UK). Identifying this mutation may be the beginning of understanding the mechanism of insulin resistance.
As part of the genetic screening work, Professor O’Rahilly’s group has also discovered that 5% of severely obese children have a mutation in another hormone receptor (the melanocortin 4 receptor). Discovery of this gene mutation has established it as the most common cause of human obesity detected to date. Again, these findings will help develop new drug targets to combat the current rapid increase in obesity in children.
9. Testosterone replacement: assessing its place in the men’s health revolution
Recent evidence suggests that androgens (including testosterone) may be protective in coronary heart disease in males. In this short symposium prominent British and American clinicians will present new data on the future potential of testosterone replacement and on the importance of androgens in coronary heart disease.
Amongst other presentations, Dr Hugh Jones (Barnsley District General Hospital) will present recent findings that demonstrate that men with coronary artery disease have lower testosterone levels than men with normal non-diseased coronary arteries. Dr Jones will also discuss the future potential of using testosterone as a treatment for common heart conditions such as angina.
There will be a high scientific content in all talks and any press attendance at the talks themselves will have to be cleared with the speakers, however you will be most welcome to attend the meeting to interview the speakers by prior arrangement. Please contact Tom Parkhill or Victoria Withy on
01454 201 612 or 07971 691 774, or via email: tom.parkhill@endocrinology.org or victoria.withy@endocrinology.org.
Please credit the Society for Endocrinology in any media coverage of this meeting.
We would be happy to provide you with general information about the Society if required.
Society for Endocrinology
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