text: Joint senior author David Bates, Professor of Oncology in the School of Medicine at The University of Nottingham, said: “Changes during the year in sex hormones made in the pituitary gland control when mammals start reproducing, and other changes like growing new coats or developing antlers. 
   
   A study, led by academics at the Universities of Nottingham and Bristol and published in the journal Proceedings of the National Academy of Sciences (PNAS), reveals the link between breeding season and the hormone melatonin, made in the pineal gland in the brain during long winter nights. 
   
   Scientists have discovered for the first time how animals link the change in seasons to their fertility. 
   
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   “The length of the day is recognised in most vertebrate animals by the pineal gland in the brain, which produces melatonin. However, until now, it has not been known how melatonin, which is produced at night, signals to the area of the pituitary gland that controls sex hormones.” 
   
   The team of scientists, which also included PhD student Dr Jennifer Castle-Miller and Dr Domingo Tortonese, in the Faculty of Health Sciences at the University of Bristol, found that in sheep, melatonin controls production of two different types of a protein called vascular endothelial growth factor (VEGF). This happens within a specific region of the pituitary gland, away from the area where sex hormones are made. 
   
   In winter, sheep make forms of VEGF that stop blood vessels growing. In summer, they make a different VEGF that makes vessels grow between the two areas of the pituitary. This allows VEGF to act as a messenger to control sex hormone-producing cells and fertility – the first time that the molecule linking long winter nights to sex hormones has been found. 
   
   The search for the missing link between the different parts of the pituitary has been going on for nearly 30 years, because knowing how this works could, for instance, help control when sheep start lambing, enabling farmers to respond to climate change. The findings also have wider implications for how animals, and potentially humans, use this system in health and disease. 
   
   The scientific paper Mechanisms Regulating Angiogenesis Underlie Seasonal Control of Pituitary Function is published by PNAS and will be available on the PNAS website after the embargo has lifted. 
   
   — Ends — 
   
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   Notes to editors: The University of Nottingham has 43,000 students and is ‘the nearest Britain has to a truly global university, with a “distinct” approach to internationalisation, which rests on those full-scale campuses in China and Malaysia, as well as a large presence in its home city.’ (Times Good University Guide 2016). It is also one of the most popular universities in the UK among graduate employers and was named University of the Year for Graduate Employment in the 2017 The Times and The Sunday Times Good University Guide. It is ranked in the world’s top 75 by the QS World University Rankings 2015/16, and 8th in the UK for research power according to the Research Excellence Framework 2014. It has been voted the world’s greenest campus for four years running, according to Greenmetrics Ranking of World Universities. 
   
   Impact: The Nottingham Campaign, its biggest-ever fundraising campaign, is delivering the University’s vision to change lives, tackle global issues and shape the future. More news… ||||| Study may reveal why melatonin affects breeding, horn growth and coat thickness – and allow farmers to change the timing of lambing season 
   
   Why do sheep get horny in winter? Because the light is baaad, says study 
   
   The mystery of why sheep get horny in the winter might have been solved, according to new research. 
   
   Scientists say they have uncovered the key to the mechanism by which changes in the length of the day prompt certain animals to begin breeding, trigger the growth of horns and even change the thickness of their coat. 
   
   The findings, the team add, could help farmers tinker with the timing of the lambing season. 
   
   “Now we know what that link is we can start to understand how it can be controlled,” said David Bates, professor of oncology at the University of Nottingham and co-author of the research. 
   
   Snow monkey attempts sex with deer in rare example of interspecies mating Read more 
   
   It has long been known that changes in animals’ fertility over the seasons is linked to melatonin – a hormone released at night from the pineal gland in the brain. This hormone acts on another gland, the pituitary, affecting the levels of various sex hormones it produces. 
   
   
   
   With the onset of fertility in sheep linked to longer periods of melatonin production, winter is the season for ovine Casanovas. But there is a puzzle. 
   
   The region of the pituitary gland that detects melatonin is separate to the region that produces sex hormones. As a result, scientists had been baffled as to how melatonin ends up affecting the onset of fertility. “No-one has been able to find what the link is,” said Bates. 
   
   Now Bates and colleagues from the University of Bristol say they have the answer. 
   
   Writing in the journal PNAS, the team reveal the missing link is a protein, known as vascular endothelial growth factor, which is made in the region of the pituitary gland that detects melatonin. 
   
   “The protein is made in two different types; it is made in a form that blocks blood vessel growth or a form that stimulates blood vessel growth,” said Bates. “Melatonin definitely controls which type [of the protein] you make.” 
   
   The team have found that the form of the protein which blocks the growth of blood vessels, reducing the connection between different regions of the pituitary gland, is triggered during long periods of melatonin production – typical of the winter. In addition, this form of the protein was found to stimulate the production of sex hormones which prompt sheep to eye up the opposite sex. 
   
   By contrast, a shorter duration of melatonin production – typical of summer – was linked to the formation of the alternative form of the protein, which increases the growth of blood vessels and acts as an anaphrodisiac. 
   
   The revelation, says Bates, could help farmers. “As climate change occurs and you start to get harsher winters, for instance, you might want to delay the breeding so the lambs are born slightly later,” he said. “So you might be able to actually increase survival of the lambs.” 
   
   Mysteries remain, however, not least the question of why the breeding season of horses, for example, falls during the spring and summer when the production of melatonin is at its lowest. 
   
   'Tinder for orangutans': Dutch zoo to let female choose mate on a tablet Read more 
   
   Andrew Loudon, a professor of animal biology at the University of Manchester who was not involved in the research, welcomed the study, pointing out that it highlights the importance of the region of the pituitary gland that detects long-term seasonal changes in melatonin. “[This] tissue contains specialised ‘calendar cells’ that act as the master regulator of seasonal cycles – so it is terribly important,” he said. “This new study offers an important insight into how the seasonal clock in this structure works to control the production of hormones in the pituitary gland.” 
   
   
   
   With similar melatonin-detecting regions present in the pituitary glands of humans, Loudon believes it is important to probe whether the newly discovered mechanism could also play a role in human biology. “Patterns of hormone secretion and also immune function are known to be seasonal in humans, although we are unusual as a species in being far less seasonal in our biology than wild animals,” he said. “However, I think it is highly likely that malfunction of these seasonal hormone-regulating pathways may well turn out to be important in the development of some endocrine diseases in the pituitary gland.” ||||| Animals need to measure the time of year so that they can anticipate and adapt to the arrival of a new season to align reproduction, as well as other vital functions critical for survival. A new study, conducted at the University of Bristol, has identified how animals measure annual time to control seasonal fertility. 
   
   In birds and mammals, this process of adaptation is mediated by the release of hormones from the pituitary gland that control multiple functions such as reproduction, the response to stress, and when the animals grow a new coat. The measurement of day length, however, and consequently time of year, is mediated by the hormone melatonin, which is released from the pineal gland during the night. Until now, how melatonin could signal to the pituitary was not understood and has been the subject of a 30-year quest. 
   
   The study, published in the journal Proceedings of the National Academy of Sciences (PNAS), undertaken by Dr Jennifer Castle-Miller, a former PhD student at the Centre for Comparative and Clinical Anatomy of the University of Bristol, and led by Dr Domingo Tortonese from the same school and Professor David Bates from the Division of Cancer and Stem Cells at the University of Nottingham, reports the mechanism by which melatonin translates the effects of day length on seasonal physiology. 
   
   Using the sheep as the experimental model, they found that the duration of melatonin secretion at night controls the production of different forms of a protein called vascular endothelial growth factor (VEGF) within a specific pituitary region that is close to the brain. VEGF forms that prevent blood-vessel growth are made in the winter, but those that stimulate it are made in the summer. 
   
   Dr Domingo Tortonese, joint senior author from Bristol’s Faculty of Health Sciences, said: “We found that this melatonin-dependent production of different forms of VEGF has two complementary effects. Firstly, it causes remodelling of the blood vessels that connect the brain with the pituitary gland, and secondly, it is used as a messenger signal to act on the cells of the pituitary that produce hormones that control seasonal fertility, which are located in a different part of the gland.” 
   
   The study has unravelled the mechanism through which animals measure time of year to allow their physiological adaptation to a changing environment. These findings have implications for the farming industry, and are anticipated to have an impact in human medicine. 
   
   Paper: 
   
   'Mechanisms regulating angiogenesis underlie seasonal control of pituitary function' by Castle-Miller J, Bates DO and Tortonese DJ is published in the Proceedings of the National Academy of Science (PNAS)
target: – "Why do sheep get frisky in winter?" isn't the beginning of a bad joke, but rather the question that jump-started a joint study by researchers at the University of Nottingham and the University of Bristol. The Guardian reports that scientists may now have an answer, one that could help farmers better control the breeding season. That answer, laid out in the journal PNAS, is a bit complicated. It's been known for some time that sheep's fertility is tied to production of the hormone melatonin, but how melatonin communicates with the pituitary gland, which shoots off sex hormones, has been a mystery. "No one has been able to find what the link is," says co-author David Bates. Until now, perhaps. Press releases from Nottingham and Bristol explain what may solve this 30-year-old puzzle: a protein made in the pituitary gland called vascular endothelial growth factor. It's made in two different forms, and scientists say melatonin controls which one surfaces. In the summer (when melatonin is in shorter supply), VEGF makes blood vessels grow and serves as a sheep-sex buzzkill of sorts. But in the winter, VEGF blocks blood vessel growth—and also appears to trigger a sex hormone spike. “Now we know what that link is we can start to understand how it can be controlled,” says Bates. In addition to helping farmers, the study could lead to developments in studying hormonal and seasonal patterns in humans in regard to endocrine diseases. (Using your smartphone right before you turn in could mess with your melatonin levels.)