̽��ֱ�� of Cambridge - Robin Carrell

Fevered imaginations

jfp40 — Wed, 29 Jan 2014 10:53:15 +0000

̽��ֱ��thyroid hormone thyroxine, which controls our day-to-day activity and was previously believed to remain at a constant level in the blood, actually fluctuates as a result of a protein which modifies the release of the hormone depending on body temperature, new research reveals. ̽��ֱ��research was published today, 29 January, in the journal Proceedings of the Royal Society B.

̽��ֱ��hormone thyroxine regulates metabolism in all mammals, including humans. If there is too much, it leads to hyperactivity, and if there is too little, it leads to dormancy. This essential hormone is carried and stored in the blood by the protein thyroxine-binding globulin (TBG).

It was previously thought that the levels of the hormone remained constant. However, the new research, led by Robin Carrell, Emeritus Professor of Haematology at the ̽��ֱ�� of Cambridge, found that when the body’s temperature rises, TBG’s affinity for thyroxine decreases, resulting in an increase of the available hormone and a subsequent increase in metabolism. If the body temperature drops, such as when an animal goes into hibernation, TBG’s affinity for thyroxine increases, resulting in a decrease in the availability of the hormone and a decrease in metabolism.

̽��ֱ��findings provide insight into the changes that occur during fevers, when the body accelerates its metabolism to counter infection and inflammation. ̽��ֱ��research shows that TBG has an inbuilt booster which gives a surge in thyroxine release as the body temperature rises above 37ºC. ̽��ֱ��study found that a body temperature of 39ºC will result in a 23 per cent increase in concentration of thyroxine levels in the blood – temporarily moving into the range seen in patients with hyperthyroidism.

Professor Carrell said: “ ̽��ֱ��effect of temperature on thyroxine levels has been largely overlooked because most measurements of the hormone are carried out when the blood is at room temperature. As a result, blood samples taken from hypothermia or heatstroke patients, or from an infant with fever, would not show the change of free thyroxine in the blood. We are excited by our findings as they are directly relevant to better understanding fevers, which, although beneficial, can pose problems, especially to young children.”

Evidence of the significance of this surge in thyroxine during fevers is demonstrated in a unique way – an environmental adaptation in the aboriginal Australian. ̽��ֱ��researchers discovered that a genetic modification in aboriginal Australians recalibrates the TBG protein’s effect during fevers and so will cancel the fever-induced boost in metabolism.

̽��ֱ��researchers believe that whilst being advantageous as a defence mechanism in temperate climates, such an increase will be a potential disadvantage in the arid climate of central Australia. There the historic survival risk has been not so much the infection itself, but rather the dehydration and heat exhaustion that accompany dysentery and other common illnesses in childhood. ̽��ֱ��two genetic mutations have become incorporated in the DNA of some 40% of West Australian aboriginals, to give a halving of the surge in metabolic activity that would otherwise take place in fevers.

̽��ֱ��research also sheds light on infant febrile seizures - convulsive episodes that often accompany the spiking fevers during early childhood. Although not typically life threatening, these seizures, which can occur in young babies, can be a terrifying experience for parents. ̽��ֱ��researchers believe that part of the reason these seizures may occur is because the brain is especially sensitive to thyroxine - rises in thyroxine result in increased brain activity, hyper-excitability and, in the extreme, convulsive seizures. ̽��ֱ��occurrence of the last in response to increased thyroxine can now be seen to have direct implications for the previously inexplicable febrile seizures which cease as soon as the infant’s body is cooled.

Additionally, the scientists believe their discovery helps explain the euphoric feeling some people experience after spending time in a sauna or hot-tub.

Professor Carrell added: “In everyday life, the accelerated release of thyroxine that will take place as the body core temperature rises to 39ºC in a sauna or hot-tub will contribute to an enhancement of the activity of body and mind: to the euphoria and to the occasional Eureka! Old figures of speech - ‘hot headedness’ and ‘fevered imagination’ – can now be seen to have a basis in science.”

New study finds links between thyroid hormones and body temperature, shedding new light on changes that occur during fevers, and euphoric feelings arising from a hot bath or sauna

In everyday life, the accelerated release of thyroxine that will take place as the body core temperature rises to 39ºC in a sauna or hot-tub will contribute to an enhancement of the activity of body and mind: to the euphoria and to the occasional Eureka!

Professor Robin Carrell

Toshiyuki IMAI

Thermometer

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Blood pressure breakthrough holds real hope

bjb42 — Thu, 07 Oct 2010 00:00:00 +0000

After 20 years of research, scientists from the ̽��ֱ�� of Cambridge have now cracked the first step in the main process that controls blood pressure. Their findings, published today in the journal Nature, are likely to have significant implications for the treatment of pre-eclampsia as well as high blood pressure (also known as hypertension).

Blood pressure is controlled by hormones called angiotensins, which cause the blood vessels to constrict. These hormones are released by the protein angiotensinogen. Until now, it was not understood how this occurred.

Dr Aiwu Zhou, a British Heart Foundation (BHF) Fellow at the ̽��ֱ�� of Cambridge, who made the breakthrough, said: "Although we primarily focused on pre-eclampsia, the research also opens new leads for future research into the causes of hypertension in general."

To make the discovery, the researchers solved the structure of angiotensinogen with the help of an extremely intense X-ray beam produced by Diamond Light Source, the UK synchrotron. Their results revealed that the protein is oxidised and changes shape

to permit ready access to angiotensinogen by an enzyme, renin. Renin cuts off the tail of the protein to release the hormone angiotensin, which then raises blood pressure.

Taking their lab results into the clinic at the ̽��ֱ�� of Nottingham, the research team showed that the amount of oxidised, and hence more active, angiotensinogen was increased in women with pre-eclampsia.

Professor Robin Carrell at the ̽��ֱ�� of Cambridge, who led the 20-year research project, explained: "During pregnancy oxidative changes can occur in the placenta. These changes, the very ones we have found stimulates the release of the hormone angiotensin and lead to increased blood pressure, can arise as the circulation in the placenta readjusts the oxygen requirements of the growing foetus with the delivery of oxygen to the placenta from the mother."

Drugs currently used to treat high blood pressure - such as ACE inhibitors - focus on the later stages of the mechanism that controls blood pressure. Today's findings, which give insight into the previously mysterious early stages of the regulation process, provide scientists with new opportunities to research novel treatments for hypertension.

Professor Peter Weissberg, Medical Director of the BHF, which largely funded the study, said: "Every year in the UK pre-eclampsia is responsible for the deaths of around six women and several hundred babies. This research is of the highest quality and offers real hope for developing strategies to prevent or treat this dangerous condition by targeting the process that these scientists have identified. And of course, although the researchers only looked at pre-eclampsia in this study, similar strategies may be useful for those people with high blood pressure that is not effectively controlled by current medicines."

High blood pressure frequently affects pregnancy. However, in 2-7 per cent of pregnancies this develops into pre-eclampsia, which threatens the health and survival of both the mother and child. In Britain, it affects about one in 20 women during pregnancy, and every year 50,000 women and 500,000 infants die globally as a result of pre-eclampsia. There is no treatment for pre-eclampsia and often the mother is either induced early or undergoes a Caesarean.

̽��ֱ��research was largely funded by the British Heart Foundation, with additional funding provided by the Medical Research Council, the Wellcome Trust and the Isaac Newton Trust.

Photo credit: House of Sims

Scientists have discovered a mechanism which raises blood pressure in pre-eclampsia, a potentially deadly condition which occurs during pregnancy.

This research is of the highest quality and offers real hope for developing strategies to prevent or treat this dangerous condition by targeting the process that these scientists have identified."

Professor Peter Weissberg, Medical Director of the BHF

Lemuel Cantos from Flickr

blood pressure

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