Avoiding the costs of testosterone: testing a novel pathway for the regulation of aggression

Testosterone, the 'male' hormone, regulates some of the most spectacular behavioural and physical traits in the animal kingdom, including aggression, bright showy ornamentation and bristling weaponry. Prevailing opinion though, is that all of this comes with a cost: circulating testosterone also disrupts immunity. Indeed, some of the most influential theories in evolutionary biology are based on the assumption that animals, including ourselves, cannot express testosterone-dependent traits such as ornaments without suffering such costs. Recent advances in neuroscience, however, raise the intriguing possibility that many animals could employ a novel pathway to regulate testosterone-dependent traits without the need to elevate circulating testosterone, and might thereby avoid these health costs. The mechanism involves a circulating molecule called DHEA, which itself has few effects but can be readily converted to testosterone within only those cells where testosterone is needed, to stimulate particular traits. While this pathway is now a key focus of biomedical research, only a handful of studies have begun to consider its wider significance, despite the profound implications that such a flexible mechanism for the regulation of testosterone-sensitive traits would have for evolutionary biology. I propose to substantially advance our understanding of the wider role that DHEA may play in the regulation of testosterone-sensitive traits and the implications of this for evolutionary biology, by providing: (i) the first experimental investigation of the role of DHEA in regulating territorial aggression in a tropical bird (ii) the first field test of the extent to which this novel pathway allows the expression of testosterone-dependent traits while avoiding the costs traditionally associated with circulating testosterone. Territorial aggression in tropical birds is a likely and widespread candidate for regulation via DHEA, as recent studies suggest that the classical role of circulating testosterone in regulating avian aggression may not apply in the tropics, where two thirds of the world's birds live. I will conduct a series of behavioural and hormonal experiments on my established study population of white-browed sparrow weavers to test the following three predictions. First, that the DHEA conversion pathway regulates territorial aggression among dominant males. Second, that the marked differences in aggression between dominant and subordinate males are due to differences in their DHEA-related physiology. Third, that using DHEA conversion to regulate aggression avoids the costs that that would otherwise arise from having high circulating testosterone levels (specifically, the disruption of immunity and parental care and increased levels of oxidative stress). Sparrow weavers are an ideal model species for this work as they can be easily caught, manipulated and observed, and I have already proven all necessary field techniques feasible. I have considerable experience leading integrative field studies of this kind and will also be collaborating with experts in avian endocrinology and oxidative stress. This is a particularly exciting research area as controversy rages in modern biology over whether the hormonal links between traits (such as aggression and immunity) are so inflexible as to constrain how organisms will evolve, particularly in response to climate change. Demonstrating a novel and general means by which animals could sever the links between testosterone-sensitive traits will therefore generate widespread interest across biology. New insights into the links between testosterone, aggression, health, ageing and parenting will also excite health professionals, social scientists and the general public. Indeed, my research to date has attracted high profile media coverage across 15 countries and I expect this work to prove no exception, facilitated by the accessible research questions and the charismatic model organism.

Prevailing opinion in evolutionary biology is that circulating testosterone (T) mediates fundamental life-history trade-offs. Our understanding derives in large part from work on temperate birds, in which T often promotes the expression of territorial aggression and sexual signals while yielding the costly disruption of immunity and oxidative balance. Indeed, that the expression of T-dependent traits entails such costs underpins one of the most influential theories in modern behavioural ecology: the T-dependent handicap hypothesis. Recent advances in neuroendocrinology, however, raise the intriguing possibility that many animals could employ an alternative pathway to regulate T-dependent traits without paying such costs; converting a circulating androgen precursor (DHEA) into T within the target tissue, to activate sex steroid receptors locally without elevating circulating T. While this 'intracrine' pathway is now a key focus of biomedical research, only a handful of studies have begun to consider its wider significance, despite the profound implications that doing so could have for evolutionary biology. I will test for the first time whether tropical birds employ this novel pathway to regulate a classically T-dependent trait, territorial aggression, while avoiding the costs that many associate with circulating T. Territorial aggression in tropical birds is a likely candidate for regulation via DHEA, as recent evidence suggests that a classical role for T in avian aggression is unlikely to apply in the tropics, where two thirds of the world's birds live. I will use behavioural and endocrine experiments on a wild tropical bird to test: (1) the role of DHEA in regulating territorial aggression; (2) the role of DHEA in mediating rank-related differences in aggression; and (3) whether regulating aggression via circulating DHEA avoids the costs commonly associated with elevated circulating T (immune suppression, oxidative stress and disruption of parental care).

Aside from the direct impact that the proposed work will have on the fields of behavioural endocrinology and evolutionary biology (see 'Beneficiaries'), the research will impact upon the following groups: * The General Public and the Economy I have a strong track record of using my accessible research field and charismatic model organisms to promote the public understanding of science. I have presented open lectures to general audiences, engaged with schools, and maximised the exposure of my findings in the international media (see Impact Plan). Research findings that stimulate the public's fascination for the natural world in this way have both quality of life and economic impacts, with the annual impact of birdwatching alone on the UK economy being estimated at some £200m (2003 IUCN-UK report 'Use of Wild Living Resources in the United Kingdom: a Review'). Cutting-edge insights into social behaviour tend to generate particular interest, doubtless due in part to their potential relevance to human societies. I will therefore maximise the impact of my proposed research by continuing to disseminate my findings through talks for general audiences and media exposure, including the authoring and illustration of popular science articles. * Schools (Teachers and Students) A key component of the Impact Plan is to engage secondary schools in both the UK and South Africa. First, we will engage directly with three secondary schools surrounding the field-site in the Kalahari and a further three partner-schools surrounding the host institution in Cornwall. We will give an introductory lecture on animal societies to each and then encourage the international exchange between the partner schools of work penned by the students about their local species. The project will stimulate a passion for asking biological questions and also highlight biodiversity on a global scale through the contrasting species that their exchanged works illustrate. Second, we will develop a web resource for secondary schools introducing and showcasing cutting edge research on animal societies, with a view to engendering a passion for biology and an awareness of how our biological understanding advances. These resources will be posted on education websites for download and use by teachers. * Early Career Scientists The project will contribute directly to the professional development of early career scientists. It will facilitate the PI's goal of establishing an independent research career and foster the RA's academic development and skill base by allowing them to obtain diverse field, laboratory and knowledge exchange skills. Each year the project will also take on and train a volunteer field assistant who will thereby gain valuable and transferable field, lab and IT skills. * Wider Research Fields, including the Social and Medical Sciences Psychologists, economists, and anthropologists seeking to understand variation in the aggressive tendencies of humans also stand to benefit from this work, as recent research has highlighted the role that circulating DHEA (rather than testosterone) may play in regulating aggression in young males, particularly those with aggressive conduct disorder. Medical researchers and practitioners may also benefit, as the mechanisms that regulate aggressive tendencies and their potential links with health, aging and parenting (all explored here) are important areas of physical and mental health research. I will maximise the impact of the proposed research on these wider fields by publishing in high impact cross-disciplinary journals, presenting the work at international inter-disciplinary conferences, and continuing to attract high profile media coverage.