̽��ֱ�� of Cambridge - hormone

High levels of oestrogen in the womb linked to autism

cjb250 — Mon, 29 Jul 2019 08:25:40 +0000

̽��ֱ��discovery adds further evidence to support the prenatal sex steroid theory of autism first proposed 20 years ago.

In 2015, a team of scientists at the ̽��ֱ�� of Cambridge and the State Serum Institute in Denmark measured the levels of four prenatal steroid hormones, including two known as androgens, in the amniotic fluid in the womb and discovered that they were higher in male foetuses who later developed autism. These androgens are produced in higher quantities in male than in female foetuses on average, so might also explain why autism occurs more often in boys. They are also known to masculinise parts of the brain, and to have effects on the number of connections between brain cells.

Today, the same scientists have built on their previous findings by testing the amniotic fluid samples from the same 98 individuals sampled from the Danish Biobank, which has collected amniotic samples from over 100,000 pregnancies, but this time looking at another set of prenatal sex steroid hormones called oestrogens. This is an important next step because some of the hormones previously studied are directly converted into oestrogens.

All four oestrogens were significantly elevated, on average, in the 98 foetuses who later developed autism, compared to the 177 foetuses who did not. High levels of prenatal oestrogens were even more predictive of likelihood of autism than were high levels of prenatal androgens (such as testosterone). Contrary to popular belief that associates oestrogens with feminisation, prenatal oestrogens have effects on brain growth and also masculinise the brain in many mammals.

Professor Simon Baron-Cohen, Director of the Autism Research Centre at the ̽��ֱ�� of Cambridge, who led this study and who first proposed the prenatal sex steroid theory of autism, said: “This new finding supports the idea that increased prenatal sex steroid hormones are one of the potential causes for the condition. Genetics is well established as another, and these hormones likely interact with genetic factors to affect the developing foetal brain.”

Alex Tsompanidis, a PhD student in Cambridge who worked on the study, said: “These elevated hormones could be coming from the mother, the baby or the placenta. Our next step should be to study all these possible sources and how they interact during pregnancy.”

Dr Alexa Pohl, part of the Cambridge team, said: “This finding is exciting because the role of oestrogens in autism has hardly been studied, and we hope that we can learn more about how they contribute to foetal brain development in further experiments. We still need to see whether the same result holds true in autistic females.”

However, the team cautioned that these findings cannot and should not be used to screen for autism. “We are interested in understanding autism, not preventing it,” added Professor Baron- Cohen.

Dr Arieh Cohen, the biochemist on the team, based at the State Serum Institute in Copenhagen, said: “This is a terrific example of how a unique biobank set up 40 years ago is still reaping scientific fruit today in unimagined ways, through international collaboration.”

̽��ֱ��research was supported by the Autism Research Trust, the Medical Research Council, and Wellcome.

Reference
Baron-Cohen, S et al. Foetal oestrogens and autism. Molecular Psychiatry; 29 July 2019; DOI: 10.1038/s41380-019-0454-9

Scientists have identified a link between exposure to high levels of oestrogen sex hormones in the womb and the likelihood of developing autism. ̽��ֱ��findings are published today in the journal Molecular Psychiatry.

This new finding supports the idea that increased prenatal sex steroid hormones are one of the potential causes for the condition

Simon Baron Cohen

Anders Printz

Me & Vincent

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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‘Believing you’re a winner’ gives men a testosterone boost and promiscuous disposition

fpjl2 — Thu, 09 Aug 2018 08:36:05 +0000

A new study shows that men only have to believe they’ve bested another man in competition to get raised testosterone levels and an inflated sense of their own value as a sexual prospect.

Scientists found that this hormonal and psychological shift made men more inclined to approach new potential partners.

̽��ֱ��research team measured hormone levels, as well as self-perceived attractiveness and confidence in approaching women, in 38 men in their twenties before and after competing in head-to-head battles on rowing machines.

Unbeknownst to participants, the competitions in the study were rigged to randomly declare the winner, regardless of who was the stronger rower.

While previous studies have shown that winning can affect male hormones, it was not known whether this was down to the efforts it takes to win or the belief that one is victorious.

̽��ֱ��latest study, led by biological anthropologists from the ̽��ֱ�� of Cambridge and published today in the journal Human Nature, reveals that just being convinced you have won, or indeed lost, is enough to cause male hormonal fluctuations that can influence sexual behaviour.

Researchers say this is an example of “plasticity”: the body adapting quickly – without altering genetic make-up – to suit a change in circumstance. In this case a perceived change in social status, due to the men believing they have defeated a rival.

̽��ֱ��body attempts to take advantage of this apparent status improvement by inducing chemical and consequently behavioural changes that promote a “short-term” approach to reproductive success, say the researchers. Namely, more sex with new and different partners.

“Much of evolution consists of trade-offs in energy investment,” said study lead author Dr Danny Longman, from Cambridge’s Department of Archaeology.

“A common trade-off for males both across and within species is between mating strategies. One reproductive approach is short-term, investing time and energy in attracting and pursuing many mates, and fighting off competition. Another approach is long-term, investing energy in raising offspring with a single mate.”

“We found that a perceived shift in social status can cause male physiology to adapt by preparing to shift mating strategies to optimise reproductive success.”

Longman points out that in many animal populations, male social hierarchies correspond with reproductive success, and social status is determined by competition between males.

̽��ֱ��study used a simple proxy for social and sexual competition by pitting athletic young men against each other to see who was the most powerful rower.

“Victory in a rowing contest strongly implies the possession of greater physical strength than the opponent, a trait found to be valued by women in our evolutionary past when choosing a mate,” said Longman.

He took saliva samples to test hormone levels before and after the races. A number of psychological questionnaires were also administered, designed to gauge self-esteem, ‘sociosexuality’ (willingness to engage in casual sex), ‘self-perceived mate value’ and mating behaviour (e.g. the likelihood of approaching attractive women). Crucially, Longman and colleagues then manipulated the results of the races.

̽��ֱ��men who believed they had won received an average testosterone increase of 4.92%, while those convinced they had lost dropped by an average of 7.24%. Overall, men who thought they were winners had testosterone levels 14.46% higher their deflated opponents.

̽��ֱ��men who thought they had lost showed no difference in their perceived value as a mate or confidence approaching women. However, the men who felt like winners had a ‘self-perceived mate value’ that was 6.53% higher, on average, than their rivals, and were 11.29% more likely to approach attractive women in an effort to instigate sexual relations.

“ ̽��ֱ��endocrine system that controls hormones is responsive to situational changes. Previous research has shown that testosterone is lower when men are in a committed relationship, or have children, to promote long-term mating strategies,” said Longman.

“Our results show that both testosterone and its corresponding psychological effects can fluctuate quickly and opportunistically, shifting towards short-term mating in response to a perceived change in status that may increase mating value.”

Male social status has less to do with physical strength in many modern societies, and Longman would be curious to see if similar results arise from intellectual challenges more familiar to the office-based culture many men now inhabit. There is always the issue of free will, however.

“Male physiology may shift to take advantage of certain situations, but ultimately a man’s decisions are up to him.”

New findings suggest that the male body tries to “optimise” self-perceived improvements in social status through hormonal shifts that promote “short-term mating”.

Our results show that both testosterone and its corresponding psychological effects can fluctuate quickly and opportunistically

Danny Longman

U.S. Army

U.S. Army World Class Athlete Program wrestler Spc. Jeremiah Davis (right) squares off against Sunkist Kids' Joe Betterman

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Women with polycystic ovary syndrome more likely to have a child with autism

cjb250 — Wed, 01 Aug 2018 12:00:44 +0000

PCOS affects about one in ten women and is caused by elevated levels of the hormone testosterone. It is associated with fluid-filled sacs (called follicles) in the ovaries, and with symptoms such as delayed onset of puberty, irregular menstrual cycles, and excess bodily hair.

Autism is a condition characterized by difficulties in social interaction and communication alongside unusually narrow interests, a strong preference for predictability, and difficulties adjusting to unexpected change. Some autistic people also have learning difficulties and delayed language, and many have sensory hyper-sensitivity. ̽��ֱ��signs of autism are evident in childhood even if the diagnosis is not made until later, and occurs in about 1% of the population.

̽��ֱ��research team previously published work in 2015 which showed that before they are born, autistic children have elevated levels of ‘sex steroid’ hormones (including testosterone) which ‘masculinise’ the baby’s body and brain. ̽��ֱ��discovery that prenatal sex steroid hormones are involved in the development of autism is one possible explanation for why autism is diagnosed more often in boys.

̽��ֱ��scientists wondered where these elevated sex steroid hormones were coming from, one possible source being the mother. If she had higher levels of testosterone than usual, as is the case in women with PCOS, then some of the hormone might cross the placenta during pregnancy, exposing her unborn baby to more of this hormone, and changing the baby’s brain development.

Using anonymous data from a large database of GP health records, the study looked at 8,588 women with PCOS and their first-born children, compared to a group of 41,127 women without PCOS. ̽��ֱ��team found that, even after taking into account other factors (like maternal mental health problems or complications during pregnancy), women with PCOS had a 2.3% chance of having an autistic child, compared with the 1.7% chance for mothers without PCOS.

̽��ֱ��team stressed that the likelihood of having an autistic child is still very low, even among women with PCOS – but finding this link provides an important clue in understanding one of the multiple causal factors in autism.

̽��ֱ��team presented their findings at the International Meeting for Autism Research in 2016, and their findings were replicated in a Swedish study in the same year, adding to the reliability of the result.

̽��ֱ��team also conducted two other studies using the same data and found that autistic women were more likely to have PCOS, and women with PCOS were more likely to have autism themselves. This strongly suggests that these two conditions are linked, probably because they both share elevated sex steroid hormone levels.

Adriana Cherskov, the Master’s student who analysed the data, and who is now studying medicine in the US, said: “This is an important piece of new evidence for the theory that autism is not only caused by genes but also by prenatal sex steroid hormones such as testosterone.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre, who supervised the research, said: “This new research is helping us understand the effects of testosterone on the developing fetal brain, and on the child’s later behaviour and mind. These hormonal effects are not necessarily independent of genetic factors, as a mother or her baby may have higher levels of the hormone for genetic reasons, and testosterone can affect how genes function.”

Dr Carrie Allison who co-supervised the research, said: “We need to think about the practical steps we can put in place to support women with PCOS as they go through their pregnancies. ̽��ֱ��likelihood is statistically significant but nevertheless still small, in that most women with PCOS won’t have a child with autism, but we want to be transparent with this new information.”

Dr Rupert Payne from the ̽��ֱ�� of Bristol Centre for Academic Primary Care, a GP and the expert on the team in using GP health record data for this type of research, said: “Autism can have a significant impact on a person’s wellbeing, and on their parents, and many autistic people have significant health, social care and educational special needs. This is an important step in trying to understand what causes autism. It is also an excellent example of the value of using anonymous routine healthcare data to answer vital medical research questions.”

̽��ֱ��study was supported by the Autism Research Trust, the Medical Research Council, Wellcome, a Gates Cambridge Trust Scholarship and Rouse Ball/Eddington Research Fund Award at Trinity College.

Reference
Cherskov, A., Pohl, A Allison, C, Zhang, H, Payne, R, and Baron-Cohen, S. Polycystic ovary syndrome and autism: A test of the prenatal sex steroid theory. Translational Psychiatry; 1 Aug 2018; DOI: 10.1038/s41398-018-0186-7

Women with polycystic ovary syndrome (PCOS) are more likely than other women to have an autistic child, according to an analysis of NHS data carried out by a team at Cambridge ̽��ֱ��’s Autism Research Centre. ̽��ֱ��research is published today in the journal Translational Psychiatry.

This is an important piece of new evidence for the theory that autism is not only caused by genes but also by prenatal sex steroid hormones such as testosterone

Adriana Cherskov

jeff_golden

In His Own World

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Plants increase flower production within a day of soil nutrient application

Anonymous — Tue, 23 Jan 2018 10:07:42 +0000

A team of plant scientists examined the processes through which plants are able to pass on information about the external environment from the roots to the new shoots. ̽��ֱ��results showed that increased soil nutrients leads to a response in stem cells in the shoots in less than 24 hours.

Experiments showed that this rapid response occurred both in vitro at the microscopic level and ex vitro with entire plants beginning to increase the rate of stem cell growth and flower development in response to the application of nitrogen in the form of nitrate.

̽��ֱ��scientists say that the study, published in Proceedings of the National Academy of Sciences, could contribute to improving crop yields by refining timing of fertiliser application and selective plant breeding.

Plant stem cells Stem cells in plants have the same function as stem cells in animals. They are undifferentiated cells that are capable of developing into specialised organ cells, such as leaves or flowers. Plant stem cells are located in the meristems of plants (growing tips of roots and shoots) and supply precursor cells from which the different parts of a plant grow from.

First author of the paper, Dr Benoit Landrein said that it was already well established that the availability of nitrate can affect various aspects of plant development. While it was known that plant hormones called cytokinins were involved in this root-to-shoot communication, the exact role of cytokinins in mediating the response of the meristem (the structure that produces all of the aerial organs of plant) to mineral nutrients had not been described before.

What are cytokinins? Cytokinins are a class of plant hormones that control many different aspects of plant development and are involved in the response of the plants to environmental signals. ̽��ֱ��hormone notably acts as a messenger between the plant’s roots and its shoots, communicating the availability of soil nutrients detected by the roots to the rest of the plant.

“Through this study, we provide an integrative model of the response of the meristem to a key environmental signal by showing that the cytokinins produced in the root in response to nutrients can modify the pool of stem cells in the meristem, which leads to a rapid change in the rate of flower production,” Dr Landrein said.

“Within one day of the root cells detecting additional nitrate, the cytokinin hormone precursors had travelled through the plant and converted to active hormones at the shoot meristem, which started influencing the shoot’s growth. ̽��ֱ��speed of this process was very surprising – the roots had not only responded to the change in environment themselves, they had rapidly communicated this information from the roots to the stem cells at the very top of the plant. We observed shoot meristem cells were starting to respond within 24 hours of the application of nitrate.”

Dr Landrein is a member of the research groups of Professor Henrik Jönsson, Dr James Locke and Professor Elliot Meyerowitz, which are working to increase our understanding of how cellular level processes in plants are controlled by gene regulatory networks, hormone transport and signalling, cell growth and division. Professor Jönsson said that while this latest research was undertaken in the plant Arabidopsis, the findings can be applied in future to crops.

“This research provides us with improved insight into how mineral nutrients influence plant architecture and could be used to better understand plant response to environmental inputs and to develop cultivars with increased yield. Crops where the same cytokinin action between roots and shoots occurs could significantly benefit from this. For example, genes involved in the regulation of cytokinins have been mapped in rice and maize and this knowledge could be utilised to select for plants with higher seed yields.”

	Arabidopsis Arabidopsis is a member of the brassica family, which includes common commercially grown crops such as oilseed rape, cabbages, kale and Brussels sprouts. While recognised by most people as a weed that is commonly seen growing on roadsides, Arabidopsis was one of the first plants to have its entire genome mapped and is used as a model for studying plant biology.

This research has been published in Proceedings of the National Academy of Sciences: Nitrate modulates stem cell dynamics in Arabidopsis shoot meristems through cytokinins. Benoit Landrein, Pau Formosa-Jordan, Alice Malivert, Christoph Schuster, Charles W. Melnyk, Weibing Yang, Colin Turnbull, Elliot M. Meyerowitz, James C. W. Locke, and Henrik Jönsson. PNAS 2018 ; published ahead of print January 23, 2018, doi:10.1073/pnas.1718670115

This research was undertaken through a collaboration between the Jönsson, Locke and Meyerowitz research groups at the Sainsbury Laboratory, ̽��ֱ�� of Cambridge.

Article by Kathy Grube, Communications Manager, Sainsbury Laboratory.

̽��ֱ��molecular mechanisms enabling plants to quickly adapt their rate of flower production in response to changing nutrient levels in soil have been revealed by researchers at the Sainsbury Laboratory.

This knowledge could be utilised to select for plants with higher seed yields

Benoit Landrein

Plant meristems

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Opinion: Losing your virginity: how we discovered that genes could play a part

Anonymous — Fri, 15 Apr 2016 08:13:05 +0000

As far as big life decisions go, choosing when to lose your virginity or the best time start a family are probably right up there for most people. It may seem that such decisions are mostly driven by social factors, such as whether you’ve met the right partner, social pressure or even your financial situation. But scientists are increasingly realising that such sexual milestones are also influenced by our genes.

In a new study of more than 125,000 people, published in Nature Genetics, we identified gene variants that affect when we start puberty, lose our virginity and have our first child. This is hugely important as the timing of these events affect educational achievements as well as physical and mental health.

Children can start puberty at any time between eight and 14-years-old. Yet it is only in recent years that we have begun to understand the biological reasons for this. Through studies of both animals and humans, we now know that there’s a complex molecular machinery in the brain that silences puberty hormones until the right time. At this point, chemical messengers secreted from the brain begin a cascade of events, leading to the production of sex hormones and reproductive maturity.

Human genetics studies have identified many genes that are linked to individual differences in the onset of puberty. There are broadly two approaches used to map such genes – studies of patients affected by rare disorders that affect puberty and large-scale population studies. ̽��ֱ��former is helpful because it can investigate gene variants that cause extremely early or delayed/absent puberty.

In previous research, we used population studies to survey a large number of individuals using questionnaires and then genome-wide association studies to scan these same participants for common genetic differences. We could then assess whether the participants' reported age at puberty was related to particular gene variants. In this way, we have in a number of studies identified more than 100 such variants, each modifying puberty timing by just a few weeks. However, together they contribute substantially.

We now understand that both nature and nurture play a roughly equal role in regulating the timing of puberty. For example, studies have consistently shown that obesity and excessive nutrition in children can cause an early onset of puberty.

Genetic factors

However, we know far less about the biological and genetic factors behind the ages that we first have sexual intercourse or have a first child. This is because previous research has focused more on environmental and family factors than genetics. But the launch of UK Biobank, a study with over half a million participants, has greatly helped to fill this lack of knowledge.

In our new study, we used this data to survey some 125,000 people in the same way as in the puberty studies. We found 38 gene variants associated with the age of first sexual intercourse. ̽��ֱ��genes that we identified fall broadly into two groups. One category is genes with known roles in other aspects of reproductive biology and pubertal development, such as the oestrogen receptors, a group of proteins found on cells in the reproductive tract and also in behaviour control centres of the brain.

If you went through puberty early you are more likely to have many children in life. Tom Adriaenssen/wikimedia, CC BY-SA

̽��ֱ��other group includes genes which play roles in brain development and personality. For example, the gene CADM2, which controls brain activity and also has strong effects on whether we regard ourselves to be risk-takers. We discovered that this gene was also associated with losing your virginity early and having a higher number of children throughout life. Similarly, the gene MSRA, linked to how irritable we are, was also associated with age at first sexual intercourse. Specifically, people who are more irritable typically have a later encounter. However, more research is needed to show exactly how these genes help regulate the timing of the reproductive milestones.

We were also able to quantify that around 25% of the variation in these milestones was due to genetic differences rather than other factors.

Implications for public health

An important reason why we study reproductive ageing is that these milestones impact reproductive outcomes and also broader health risks. Epidemiological studies show that individuals who go through puberty at younger ages have higher risks of many diseases of old age, such as diabetes, heart disease and breast cancer. Similarly, first sexual intercourse at an earlier age is linked to a number of adverse behavioural, educational and health outcomes.

Using a statistical genetics approach called Mendelian Randomisation, a technique that helps clarify the causal relationship between human characteristics, these studies can tell us whether such epidemiological associations are likely to be causal rather than just random associations. We managed to show that early puberty actually contributes to a higher likelihood of risk-taking behaviours, such as sexual intercourse at an earlier age. It was also linked to having children earlier, and having more children throughout life.

These findings, along with previous studies linking early puberty and loss of virginity to social and health risks, back the idea that future public health interventions should aim to help children avoid early puberty, for example by diet and physical activity and avoiding excess weight gain. Our findings predict that this would have benefits both on improving adolescent health and educational outcomes and also for future health at older ages.

John Perry, Senior Investigator Scientist, ̽��ֱ�� of Cambridge and Ken Ong, Group Leader of the Development Programme at the MRC Epidemiology Unit, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

John Perry and Ken Ong (MRC Epidemiology Unit) discuss how sexual milestones are influenced by our genes and how this can impact on broader health risks.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Breast cancer genetic variants found to alter how cells respond to oestrogen

cjb250 — Mon, 29 Feb 2016 16:52:02 +0000

Breast cancer is the most common type of cancer among women. Around one in eight women in the general population is expected to develop the disease at some point in her life. ̽��ֱ��majority of cases occur in women aged 50 and over.

̽��ֱ��female sex hormone oestrogen acts as a trigger, binding to a molecule known as an oestrogen receptor in most breast cells and triggering a cascade of signals that cause the cell to behave normally. However, the oestrogen receptor is switched off in some cells and these do not respond to the hormone.

An international collaboration, led by researchers at the ̽��ֱ�� of Cambridge and the QIMR Berghofer Medical Research Institute, examined the DNA surrounding the gene for the oestrogen receptor – known as ESR1 – in women with different types of breast cancer against those of healthy controls to identify genetic variants responsible for an increased risk of breast cancer. ̽��ֱ��results are published today in the journal Nature Genetics.

Among their findings, the researchers discovered five cancer-risk variants based within or around the ESR1 gene. This gene has long been known to be related to the risk and progress of breast cancer, but little is understood of how it works and why it should affect breast cancer.

Of the five variants discovered by the team, four were more strongly associated with tumours where the ESR1 gene is switched off, so the tumour cells have no oestrogen receptors. These represent around one fifth of breast cancers.

One of these four variants was of particular interest as it was associated with a rarer type of breast tumour that contain active receptors for the protein known as ‘human epidermal growth factor 2’ (HER2). Such tumours can be treated by the drug trastuzumab (marketed as Herceptin). This is believed to be the first time a specific genetic risk factor for HER2 positive breast tumours has been found.

Dr Stacey Edwards’ team from QIMR Berghofer, Brisbane, had been searching for gene regulatory elements around the ESR1 gene, which act like the volume controls on a radio or TV, turning the activity of the nearby genes up or down. There are two major types of gene regulators: ‘enhancers’, which increase activity of the genes express such that they make more protein, and ‘silencers’, which have the opposite effect.

When the Cambridge and Brisbane teams compared notes, they spotted that four of the breast cancer risk variants coincided with ‘volume-up’ enhancers. These particular regulators did not just affect the ESR1 gene but also other nearby genes. ̽��ֱ��variants that increased risk of breast cancer directly reduced the effectiveness of each enhancer, hence turning down the volume of ESR1 and the other nearby genes. This reduced the amount of oestrogen receptor produced by breast cells.

̽��ֱ��researchers say that their results suggest the ESR1 gene works with other nearby genes to affect breast cancer development.

̽��ֱ��fifth genetic variant was found to be more strongly associated with tumours where the oestrogen receptor is switched on. This variant coincides with and alters the effectiveness of ‘volume-down’ silencer, which means that it increases the amount of oestrogen receptor protein produced by breast cells.

“It’s interesting that all five of the genetic variants that we have found affect levels of oestrogen receptors in breast cells,” says Dr Alison Dunning from the Department of Oncology at the ̽��ֱ�� of Cambridge, one of the lead authors on the study. “This suggests that there may be a ‘Goldilocks’ level of these receptors in breast cells: too few or too many and the breast cells are more likely to become cancerous.”

“As our research looks at how tumours with and without the oestrogen receptor are regulated, it’s possible it could help make sense of the enduring mystery of how tamoxifen works and why tumours develop in these two divergent ways,” says Dr Edwards, one of the study’s senior authors. “Our findings could open the way to developing new, more specific breast cancer preventions.”

̽��ֱ��genetic variants are all very common, each one carried by around one in three women. Each variant only increases the risk of developing breast cancer by a small amount.

Professor Doug Easton, another senior author from the ̽��ֱ�� of Cambridge, adds: “breast cancer is a very complex disease, with many genes, and other factors, contributing to an overall increased risk of developing the disease. These five common variants that we have identified will contribute to an eventual predictive test for breast cancer risk, and for determining the risk of the particular subtype of breast cancer, that will include hundreds of similar variants.”

Funding for the study came from organisations including the European Union, Cancer Research UK, the National Health and Medical Research Council of Australia and the Australian National Breast Cancer Foundation.

Dr Alan Worsley, Cancer Research UK’s senior science information officer, said: “We know that hundreds of genes are likely to play a role in how cancers start. And this latest study adds more detail to our genetic map of breast cancer risk, potentially helping understand which type of breast cancer is likely to develop based on a woman’s genetic makeup. Understanding more about each individual’s risk of cancer could help us find ways to potentially prevent the disease or pick it up in its earliest stages."

Reference
Dunning, AM et al. Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1. RMND1 and CCDC170. Nature Genetics; published online 29 Feb 2016. DOI: 10.1038/ng.3521.

An international study of almost 120,000 women has newly identified five genetic variants affecting risk of breast cancer, all of which are believed to influence how breast cells respond to the female sex hormone oestrogen.

There may be a ‘Goldilocks’ level of oestrogen receptors in breast cells: too few or too many and the breast cells are more likely to become cancerous

Alison Dunning

williami5

Breast cancer reflection

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Children with autism have elevated levels of steroid hormones in the womb

cjb250 — Tue, 03 Jun 2014 08:00:00 +0000

̽��ֱ��team of researchers, led by Professor Simon Baron-Cohen and Dr Michael Lombardo in Cambridge and Professor Bent Nørgaard-Pedersen in Denmark, utilized approximately 19,500 amniotic fluid samples stored in a Danish biobank from individuals born between 1993-1999. Amniotic fluid surrounds the baby in the womb during pregnancy and is collected when some women choose to have an amniocentesis around 15-16 weeks of pregnancy. This coincides with a critical period for early brain development and sexual differentiation, and thus allows scientists access into this important window in fetal development. ̽��ֱ��researchers identified amniotic fluid samples from 128 males later diagnosed with an autism spectrum condition and matched these up with information from a central register of all psychiatric diagnoses in Denmark.

Within the amniotic fluid the researchers looked at four key ‘sex steroid’ hormones that are each synthesized, step-by-step from the preceding one*. They also tested the steroid hormone cortisol that lies outside this pathway. ̽��ֱ��researchers found that levels of all steroid hormones were highly associated with each other and most importantly, that the autism group on average had higher levels of all steroid hormones, compared to a typically developing male comparison group. ̽��ֱ��results of the study, which was funded by the Medical Research Council, are published today in the journal Molecular Psychiatry.

Professor Baron-Cohen said: “This is one of the earliest non-genetic biomarkers that has been identified in children who go on to develop autism. We previously knew that elevated prenatal testosterone is associated with slower social and language development, better attention to detail, and more autistic traits. Now, for the first time, we have also shown that these steroid hormones are elevated in children clinically diagnosed with autism. Because some of these hormones are produced in much higher quantities in males than in females, this may help us explain why autism is more common in males.”

He added: “These new results are particularly striking because they are found across all the subgroups on the autism spectrum, for the first time uniting those with Asperger Syndrome, classic autism, or Pervasive Developmental Disorder Not-Otherwise-Specified. We now want to test if the same finding is found in females with autism.”

Dr Michael Lombardo said: “This result potentially has very important implications about the early biological mechanisms that alter brain development in autism and also pinpoints an important window in fetal development when such mechanisms exert their effects.”

Steroid hormones are particularly important because they exert influence on the process of how instructions in the genetic code are translated into building proteins. ̽��ֱ��researchers believe that altering this process during periods when the building blocks for the brain are being laid down may be particularly important in explaining how genetic risk factors for autism get expressed.

Dr Lombardo adds: “Our discovery here meshes nicely with other recent findings that highlight the prenatal period around 15 weeks gestation as a key period when important genetic risk mechanisms for autism are working together to be expressed in the developing brain.”

Professor Baron-Cohen said: “These results should not be taken as a reason to jump to steroid hormone blockers as a treatment as this could have unwanted side effects and may have little to no effect in changing the potentially permanent effects that fetal steroid hormones exert during the early foundational stages of brain development.”

He cautioned further: “Nor should these results be taken as a promising prenatal screening test. There is considerable overlap between the groups and our findings showed differences found at an average group level, rather than at the level of accurately predicting diagnosis for individuals. ̽��ֱ��value of the new results lies in identifying key biological mechanisms during fetal development that could play important roles in atypical brain development in autism.”

*Within the amniotic fluid the researchers looked at 4 key ‘sex steroid’ hormones that are each synthesized, step-by-step from the preceding one, in the ‘Δ4 sex steroid’ pathway: progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone.

Children who later develop autism are exposed to elevated levels of steroid hormones (for example testosterone, progesterone and cortisol) in the womb, according to scientists from the ̽��ֱ�� of Cambridge and the Statens Serum Institute in Copenhagen, Denmark. ̽��ֱ��finding may help explain why autism is more common in males than females. However, the researchers caution it should not be used to screen for the condition.

This is one of the earliest non-genetic biomarkers that has been identified in children who go on to develop autism

Simon Baron-Cohen

John "Jay" Glenn

I Think... therefore I am more than a diagnosis. (Cropped image)

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Novel genetic mutations cause low metabolic rate and obesity

sj387 — Fri, 25 Oct 2013 07:43:45 +0000

Researchers from the ̽��ֱ�� of Cambridge have discovered a novel genetic cause of severe obesity which, although relatively rare, demonstrates for the first time that genes can reduce basal metabolic rate – how the body burns calories.

Previous studies (performed by David Powell and colleagues at Lexicon Pharmaceuticals in Texas) demonstrated that when the gene KSR2 (Kinase Suppressor of Ras 2) was deleted in mice, the animals became severely obese. As a result of this research, Professor Sadaf Farooqi from the ̽��ֱ�� of Cambridge’s Wellcome Trust-MRC Institute of Metabolic Science decided to explore whether KSR2 mutations might also lead to obesity in humans.

In collaboration with Dr Ines Barroso’s team at the Wellcome Trust Sanger Institute, the researchers sequenced the DNA from over 2,000 severely obese patients and identified multiple mutations in the KSR2 gene. ̽��ֱ��research was published online today, 24 October, in the journal Cell.

KSR2 belongs to a group of proteins called scaffolding proteins which play a critical role in ensuring that signals from hormones such as insulin are correctly processed by cells in the body to regulate how cells grow, divide and use energy. To investigate how KSR2 mutations might lead to obesity, Professor Farooqi’s team performed a series of experiments which showed that many of the mutations disrupt these cellular signals and, importantly, reduce the ability of cells to use glucose and fatty acids.

Patients who had the mutations in KSR2 had an increased drive to eat in childhood, but also a reduced metabolic rate, indicating that they have a reduced ability to use up all the energy that they consume. A slow metabolic rate can be found in people with an underactive thyroid gland, but in these patients thyroid blood tests were in the normal range - eliminating this as a possible explanation for their low metabolic rate. People have speculated for a long time that some individuals may burn calories more slowly than others. ̽��ֱ��findings in this study provide the first evidence that defects in a particular gene, KSR2, can affect a person’s metabolic rate and how their bodies processed calories.

Professor Farooqi said: “Up until now, the genes we have identified that control body weight have largely affected appetite. However, KSR2 is different in that it also plays a role in regulating how energy is used in the body. In the future, modulation of KSR2 may represent a useful therapeutic strategy for obesity and type 2 diabetes.”

Changes in diet and levels of physical activity underlie the recent increase in obesity in the UK and worldwide. However, there is a lot of variation in how much weight people gain. This variation between people is largely influenced by genetic factors, and many of the genes involved act in the brain. ̽��ֱ��discovery of a new obesity gene, KSR2, adds another level of complexity to the body’s mechanisms for regulating weight. ̽��ֱ��Cambridge team is continuing to study the genetic factors influencing obesity, findings which they hope to translate into beneficial therapies in the future.

Professor Farooqi’s research was funded by the Wellcome Trust.

Researchers believe the gene could be a useful therapeutic target for treating obesity and type 2 diabetes

In the future, modulation of KSR2 may represent a useful therapeutic strategy for obesity and type 2 diabetes

Sadaf Farooqi

Shaury Nash

DNA code

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