Prof Iain Clarke - Researcher Profile

Iain Clarke

Address

Department of Physiology
Faculty of Medicine, Nursing & Health Sciences, Clayton

Biography

 

Thermogenesis a key to pre-disposition for obesity

Professor Iain Clarke is overseeing a multi-pronged approach to physiology research. The head of the Department of Physiology, he has focused his department on several key pillars including neuroendocrinology, obesity, diabetes, cardiovascular/kidney disease and sensory and autonomic neuroscience. Iain’s main area of research is neuroendocrinology, which relates to the interaction between the nervous and hormonal systems. He has recently made two discoveries that could change how we view fertility and obesity.

 

 

Iain is interested in how the brain and pituitary gland control reproduction, appetite and energy expenditure, and how this relates to obesity and fertility. With regard to the obesity issue, he believes we should be focussing on appetite. 

“Three large studies involving thousands of people have been done around the world, where a program of diet and exercise was imposed,” Iain explains. “Certainly, people lost weight on those programs, but as soon as it stopped, they went right back to where they were at the start. There’s an inherent problem in trying to solve the obesity problem by controlling food intake; it just doesn’t work. Everybody has a homeostatic set-point that is determined by the genes they inherited from their parents. Other factors can impact on that, but by and large it’s genetic.”

Iain’s solution to this problem is to focus on energy expenditure. The body breaks this down into various components, one of which thermogenesis. Iain believes this process is vital in determining whether an individual has a predisposition to obesity.

“Traditionally thermogenesis was thought to only exist in newborns, but we know now it exists in adults as well. After lunch you feel warm and drowsy because your temperature has risen through postprandial thermogenesis. We’ve shown that some individuals have very high postprandial thermogenesis and some have very low postprandial thermogenesis. Those with low levels become overweight and those with high levels do not. We can also apply a test and say ‘you’re going to become overweight and you’re not’, which is a major breakthrough. The next step is to find a way to manipulate heat production,” he says. 

Iain has also identified peptides in the brain that have both positive and negative effects on reproduction.  In collaboration with Dr Jeremy Smith, Iain is investigating the use of these agents in a range of situations of infertility and fertility. Iain is most excited by the gonadotropin-inhibitory hormone, which is also related to the issue of food intake. 

“This peptide consists of only eight amino acids, but intravenous infusion can block ovulation. If you squirt it into the brain, it doubles food intake within two hours. It inhibits reproduction and stimulates food intake, so it could be a molecular switch in the brain. We know that food intake is lower in human females at the time of ovulation, and that’s when the levels of these peptides are at their lowest. There’s a reduction in the negative effect on reproduction that allows that to happen and a reduction in the stimulatory effect of feeding, which reduces appetite,” Iain explains.

Iain is also collaborating with Helen Truby from the Department of Nutrition and Dietetics and Shantha Rajaratnam from the School of Psychology and Psychiatry to create a translational physiology unit at Notting Hill. He says this facility will offer dynamic multi-disciplinary research opportunities.

“It puts a nutrition/dietetics kitchen beside a sleep lab and an exercise physiology lab. Those three areas will interact and the work will be done in humans. It will become operational in 2012 and I want to engage everyone to use it.”

 

Keywords

Neuroendocrinology, Reproduction, Metabolic Neuroscience, Large Animal Models, Hypothalamus

Qualifications

DOCTOR OF PHILOSOPHY
Institution: Unknown
Year awarded: 1977

Publications

Book Chapters

Clarke, I.J., Tilbrook, A.J., 2008, Gonadotropin, neural and hormonal control, in Encyclopedia of Neuroscience, eds Larry R Squire, Elsevier Ltd, USA, pp. 959-965.

Clarke, I.J., 2008, Models of 'Obesity' in large animals and birds, in Obesity & Metabolism, eds M Korbonits, Karger, Basel Switzerland, pp. 107-117.

Henry, B.A., Clarke, I.J., 2007, Food intake and stress, non-human, in Encyclopedia of Stress, eds G Fink, Academic Press, USA, pp. 162-165.

McKinley, M.J., Clarke, I.J., Oldfield, B.J., 2004, Circumventricular Organs, in The Human Nervous System, eds G Paxinos & JK Mai, Elsevier Academic Press, USA, pp. 562-591.

Clarke, I.J., 2002, Two decades of measuring GnRH secretion, in Reproduction: Large Mammals as Neuroendocrine Models, eds D C Skinner, N P Evans and C Doberska, Society for Reproduction and Fertility, Cambridge, United Kingdom, pp. 1-13.

Clarke, I.J., Tilbrook, A.J., 2000, Ovulation is timed by the brain, in Hormones and Women's Health - The Reproductive Years, Harwood Academic Press, Singapore, pp. 37-48.

Journal Articles

Clarke, S.D., Clarke, I.J., Rao, A., Evans, R.G., Henry, B.A., 2013, Differential Effects of Acute and Chronic Estrogen Treatment on Thermogenic and Metabolic Pathways in Ovariectomized Sheep, Endocrinology [P], vol 154, issue 1, The Endocrine Society, USA, pp. 184-192.

de Bond, J.P., Li, Q., Millar, R.P., Clarke, I.J., Smith, J.T., 2013, Kisspeptin Signaling Is Required for the Luteinizing Hormone Response in Anestrous Ewes following the Introduction of Males, PLoS ONE [P], vol 8, issue 2, Public Library of Science, USA, pp. 1-11.

Smith, J.T., Young, I.R., Veldhuis, J.D., Clarke, I.J., 2012, Gonadotropin-inhibitory hormone (GnIH) secretion into the ovine hypophyseal portal system, Endocrinology [P], vol 153, issue 7, The Endocrine Society, USA, pp. 3368-3375.

Clarke, I.J., Smith, J.T., Henry, B.A., Oldfield, B.J., Stefanidis, A., Millar, R.P., Puspita Sari, I., Chng, K., Fabre-Nys, C., Caraty, A., Ang, B., Chan, L., Fraley, G.S., 2012, Gonadotropin-inhibitory hormone is a hypothalamic peptide that provides a molecular switch between reproduction and feeding, Neuroendocrinology [P], vol 95, issue 4, S. Karger AG, Switzerland, pp. 305-316.

Beil, F.T., Oheim, R., Barvencik, F., Hissnauer, T.N., Pestka, J.M., Ignatius, A., Rueger, J.M., Schinke, T., Clarke, I.J., Amling, M., Pogoda, P., 2012, Low turnover osteoporosis in sheep induced by hypothalamic-pituitary disconnection, Journal of Orthopaedic Research [P], vol 30, issue 8, John Wiley & Sons, Inc., USA, pp. 1254-1262.

Adler, E.S., Hollis, J.H., Clarke, I.J., Grattan, D.R., Oldfield, B.J., 2012, Neurochemical characterization and sexual dimorphism of projections from the brain to abdominal and subcutaneous white adipose tissue in the rat, Journal Of Neuroscience [P], vol 32, issue 45, Society for Neurosciences, USA, pp. 15913-15921.

Clarke, S.D., Lee, K., Andrews, Z.B., Bischof, R., Fahri, F., Evans, R.G., Clarke, I.J., Henry, B.A., 2012, Postprandial heat production in skeletal muscle is associated with altered mitochondrial function and altered futile calcium cycling, American Journal of Physiology - Regulatory Integrative and Comparative Physiology [E], vol 303, issue 10, American Physiological Society, USA, pp. R1071-R1079.

Li, Q., Rao, A., Clarke, I.J., Smith, J.T., 2012, Seasonal variation in the gonadotropin-releasing hormone response to kisspeptin in sheep: Possible kisspeptin regulation of the kisspeptin receptor, Neuroendocrinology [P], vol 96, issue 3, S. Karger AG, Switzerland, pp. 212-221.

Clarke, S.D., Clarke, I.J., Rao, A., Cowley, M.A., Henry, B., 2012, Sex differences in the metabolic effects of testosterone in sheep, Endocrinology [P], vol 153, issue 1, The Endocrine Society, USA, pp. 123-131.

Oheim, R., Beil, F.T., Barvencik, F., Egermann, M., Amling, M., Pogoda, P., Clarke, I.J., 2012, Targeting the lateral but not the third ventricle induces bone loss in ewe: an experimental approach to generate an improved large animal model of osteoporosis, The Journal of Trauma and Acute Care Surgery [E], vol 72, issue 3, Lippincott Williams & Wilkins, USA, pp. 720-726.

Henry, B., Andrews, Z., Rao, A., Clarke, I., 2011, Central leptin activates mitochondrial function and increases heat production in skeletal muscle, Endocrinology [P], vol 152, issue 7, Endocrine Society, USA, pp. 2609-2618.

Clarke, I.J., 2011, Control of GnRH secretion: One step back, Frontiers In Neuroendocrinology [P], vol 32, issue 3, Academic Press, USA, pp. 367-375.

Sabin, M., Yau, S., Russo, V., Clarke, I., Dunshea, F., Chua, J., Cox, M., Werther, G., 2011, Dietary monounsaturated fat in early life regulates IGFBP2: Implications for fat mass accretion and insulin sensitivity, Obesity [P], vol 19, issue 12, Nature Publishing Group, USA, pp. 2374-2381.

Papargiris, M., Rivalland, E.T.A., Clarke, I.J., Smith, J.T., Pereira, A., Tilbrook, A.J., 2011, Evidence that RF-amide related peptide-3 is not a mediator of the inhibitory effects of psychosocial stress on gonadotrophin secretion in ovariectomised ewes, Journal of Neuroendocrinology [P], vol 23, issue 3, Wiley-Blackwell Publishing Ltd, UK, The Netherland, USA, pp. 208-215.

Li, Q., Rao, A., Pereira, A., Clarke, I., Smith, J., 2011, Kisspeptin cells in the ovine arcuate nucleus express prolactin receptor but not melatonin receptor, Journal of Neuroendocrinology [P], vol 23, issue 10, Wiley-Blackwell, USA, pp. 871-882.

Smith, J.T., Li, Q., Yap, K.S., Shahab, M., Roseweir, A.K., Millar, R.P., Clarke, I.J., 2011, Kisspeptin is essential for the full preovulatory LH surge and stimulates GnRH release from the isolated ovine median eminence, Endocrinology [P], vol 152, issue 3, The Endocrine Society, USA, pp. 1001-1012.

Szymanski, L., Schneider, J., Satragno, A., Dunshea, F., Clarke, I., 2011, Mesenteric infusion of a volatile fatty acid prevents body weight loss and transiently restores luteinising hormone pulse frequency in ovariectomised, food-restricted ewes, Journal of Neuroendocrinology [P], vol 23, issue 8, Wiley-Blackwell, USA, pp. 699-710.

Henry, B.A., Blache, D., Dunshea, F.R., Clarke, I.J., 2010, Altered "set-point" of the hypothalamus determines effects of cortisol on food intake, adiposity, and metabolic substrates in sheep, Domestic Animal Endocrinology [P], vol 38, Elsevier Inc., USA, pp. 46-56.

Tschop, J., Nogueiras, R., Lockie, S.K.H., Kasten, K.R., Castaneda, T.R., Huber, N., Guanciale, K., Perez-Tilve, D., Habegger, K., Ottaway, N., Woods, S.C., Oldfield, B., Clarke, I., Chua Jr, S., Farooqi, I.S., O'Rahilly, S., Caldwell, C.C., Tschop, M.H., 2010, CNS leptin action modulates immune response and survival in sepsis, Journal Of Neuroscience [P], vol 30, issue 17, Society for Neuroscience, USA, pp. 6036-6047.

Laker, R.C., Henry, B.A., Wadley, G.D., Clarke, I.J., Canny, B.J., McConell, G.K., 2010, Central infusion of leptin does not increase AMPK signaling in skeletal muscle of sheep, American Journal Of Physiology-Regulatory Integrat..., vol 300, issue 2, American Physiological Society, USA, pp. R511-R518.

Soga, T., Wong, D., Clarke, I., Parhar, I., 2010, Citalopram (antidepressant) administration causes sexual dysfunction in male mice through RF-amide related peptide in the dorsomedial hypothalamus, Neuropharmacology [P], vol 59, issue 1-2, Pergamon, Oxford United Kingdom, pp. 77-85.

Henry, B.A., Blache, D., Rao, A., Clarke, I.J., Maloney, S.K., 2010, Disparate effects of feeding on core body and adipose tissue temperatures in animals selectively bred for Nervous or Calm temperament, American Journal Of Physiology-Regulatory Integrative And Comparative Physiology [P], vol 299, issue 3, American Physiological Society, USA, pp. R907-R917.

Pereira, A., Rawson, J.A., Jakubowska, A.E., Clarke, I.J., 2010, Estradiol-17beta-responsive A1 and A2 noradrenergic cells of the brain stem project to the bed nucleus of the stria terminalis in the ewe brain: A possible route for regulation of gonadotropin releasing hormone cells, Neuroscience [P], vol 165, Pergamon, UK , France, pp. 758-773.

Anukulkitch, C., Rao, A., Pereira, A., McEwan, J., Clarke, I.J., 2010, Expression of genes for appetite-regulating peptides in the hypothalamus of genetically selected lean and fat sheep, Neuroendocrinology [P], vol 91, S. Karger AG, Switzerland, pp. 223-238.

Smith, J.T., Clarke, I.J., 2010, Gonadotropin inhibitory hormone function in mammals, Trends in Endocrinology and Metabolism [P], vol 21, issue 4, Elsevier Ltd, UK, pp. 255-260.

Smith, J.T., Shahab, M., Pereira, A., Pau, K.F., Clarke, I.J., 2010, Hypothalamic expression of KISS1 and gonadotropin inhibitory hormone genes during the menstrual cycle of a non-human primate, Biology Of Reproduction [P], vol 83, issue 4, Society for the Study of Reproduction, USA, pp. 568-577.

Backholer, K., Smith, J.T., Rao, A., Pereira, A., Iqbal, J., Ogawa, S., Li, Q., Clarke, I.J., 2010, Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells, Endocrinology [P], vol 151, issue 5, The Endocrine Society, USA, pp. 2233-2243.

Backholer, K., Bowden, M., Gamber, K., Bjorbaek, C., Iqbal, J., Clarke, I.J., 2010, Melanocortins mimic the effects of leptin to restore reproductive function in lean hypogonadotropic ewes, Neuroendocrinology [P], vol 91, S. Karger AG, Switzerland, pp. 27-40.

Smith, J.T., Clarke, I.J., 2010, Seasonal breeding as a neuroendocrine model for puberty in sheep, Molecular and Cellular Endocrinology [P], vol 324, issue 1-2, Elsevier Ireland Ltd, Ireland, pp. 102-109.

Turner, A.I., Rivalland, E.T.A., Clarke, I.J., Tilbrook, A.J., 2010, Stressor specificity of sex differences in hypothalamo-pituitary-adrenal axis activity: Cortisol responses to exercise, endotoxin, wetting, and isolation/restraint stress in gonadectomized male and female sheep, Endocrinology [P], vol 151, issue 9, The Endocrine Society, USA, pp. 4324-4331.

Clarke, I.J., Henry, B.A., 2010, Targeting energy expenditure in muscle as a means of combating obesity, Clinical And Experimental Pharmacology And Physio..., vol 37, Wiley-Blackwell Publishing Asia, Australia, pp. 121-124.

Qi, Y., Henry, B.A., Oldfield, B.J., Clarke, I.J., 2010, The action of leptin on appetite-regulating cells in the ovine hypothalamus: Demonstration of direct action in the absence of the arcuate nucleus, Endocrinology [P], vol 151, issue 5, The Endocrine Society, USA, pp. 2106-2116.

Clarke, I.J., 2010, Whichever way weight goes, inflammation shows, Endocrinology [P], vol 151, issue 3, The Endocrine Society, USA, pp. 846-848.

Anukulkitch, C., Rao, A., Dunshea, F.R., Clarke, I.J., 2009, A test of the lipostat theory in a seasonal (ovine) model under natural conditions reveals a close relationship between adiposity and melanin concentrating hormone expression, Domestic Animal Endocrinology, vol 36, issue 3, Elsevier Inc., USA, pp. 138-151.

Qi, Y., Namavar, M.R., Iqbal, J., Oldfield, B.J., Clarke, I.J., 2009, Characterization of the projections to the hypothalamic paraventricular and periventricular nuclei in the female sheep brain, using retrograde tracing and immunohistochemistry, Neuroendocrinology [P], vol 90, issue 1, S. Karger AG, Switzerland, pp. 31-53.

Pierce, B.N., Clarke, I.J., Turner, A.I., Rivalland, E.T.A., Tilbrook, A.J., 2009, Cortisol disrupts the ability of estradiol-17beta to induce the LH surge in ovariectomized ewes, Domestic Animal Endocrinology [P], vol 36, issue 4, Elsevier Inc., USA, pp. 202-208.

Oakley, A.E., Breen, K.M., Clarke, I.J., Karsch, F.J., Wagenmaker, E.R., Tilbrook, A.J., 2009, Cortisol reduces gonadotropin-releasing hormone pulse frequency in follicular phase ewes: Influence of ovarian steroids, Endocrinology, vol 150, The Endocrine Society, United States, pp. 341-349.

Roseweir, A.K., Kauffman, A.S., Smith, J.T., Guerriero, K.A., Morgan, K., Pielecka-Fortuna, J., Pineda, R., Gottsch, M.L., Tena-Sempere, M., Moenter, S.M., Terasawa, E., Clarke, I.J., Steiner, R.A., Millar, R.P., 2009, Discovery of potent kisspeptin antagonists delineate physiological mechanisms of gonadotropin regulation, The Journal of Neuroscience, vol 29, issue 12, Society for Neuroscience, USA, pp. 3920-3929.

Puspita Sari, I., Rao, A., Smith, J.T., Tilbrook, A.J., Clarke, I.J., 2009, Effect of RF-amide-related peptide-3 on luteinizing hormone and follicle-stimulating hormone synthesis and secretion in ovine pituitary gonadotropes, Endocrinology [P], vol 150, issue 12, The Endocrine Society, USA, pp. 5549-5556.

Pierce, B.N., Stackpole, C.A., Breen, K.M., Clarke, I.J., Karsch, F.J., Rivalland, E.T.A., Turner, A.I., Caddy, D.J., Wagenmaker, E.R., Oakley, A.E., Tilbrook, A.J., 2009, Estradiol enables cortisol to act directly upon the pituitary to suppress pituitary responsiveness to GnRH in sheep, Neuroendocrinology, vol 89, S. Karger AG, Switzerland, pp. 86-97.

Iqbal, J., Latchoumanin, O.A.L., Puspita Sari, I., Lang, R.J., Coleman, H.A., Parkington, H.C., Clarke, I.J., 2009, Estradiol-17beta inhibits gonadotropin-releasing hormone-induced Ca 2+ in gonadotropes to regulate negative feedback on luteinizing hormone release, Endocrinology [P], vol 150, issue 9, The Endocrine Society, USA, pp. 4213-4220.

Clarke, I.J., Qi, Y., Puspita Sari, I., Smith, J.T., 2009, Evidence that RF-amide related peptides are inhibitors of reproduction in mammals, Frontiers in Neuroendocrinology, vol 30, issue 3, Academic Press, USA, pp. 371-378.

Haylor, J.L., Parker, E., Risbridger, G.P., Beale, D., Brown, B.L., Dobson, P.R.M., Clarke, I.J., Hart, J.E., 2009, Inhibition of compensatory renal growth by the N-terminus of a sheep-derived peptide, Regulatory Peptides [P], vol 152, issue 1-3, Elsevier Science BV, The Netherlands, pp. 48-53.

Clarke, I.J., Smith, J.T., Caraty, A., Goodman, R.L., Lehman, M.N., 2009, Kisspeptin and seasonality in sheep, Peptides, vol 30, Elsevier Inc., United States, pp. 154-163.

Smith, J.T., Li, Q., Pereira, A., Clarke, I.J., 2009, Kisspeptin neurons in the ovine arcuate nucleus and preoptic area are involved in the preovulatory luteinizing hormone surge, Endocrinology [P], vol 150, issue 12, The Endocrine Society, USA, pp. 5530-5538.

Backholer, K., Smith, J.T., Clarke, I.J., 2009, Melanocortins may stimulate reproduction by activating orexin neurons in the dorsomedial hypothalamus and kisspeptin neurons in the preoptic area of the ewe, Endocrinology [P], vol 150, issue 12, The Endocrine Society, USA, pp. 5488-5497.

Qi, Y., Oldfield, B.J., Clarke, I.J., 2009, Projections of RFamide-related peptide-3 neurones in the ovine hypothalamus, with special reference to regions regulating energy balance and reproduction, Journal of Neuroendocrinology [P], vol 21, issue 8, Wiley-Blackwell Publishing Ltd, UK, USA, pp. 690-697.

Smith, J.T., Saleh, S.N., Clarke, I.J., 2009, Seasonal and cyclical change in the luteinizing hormone response to kisspeptin in the ewe, Neuroendocrinology [P], vol 90, issue 3, S. Karger AG, Switzerland, pp. 283-291.

Henry, B.A., Clarke, I.J., 2008, Adipose tissue hormones and the regulation of food intake, Journal of Neuroendocrinology, vol 20, issue 6, Wiley-Blackwell Publishing Ltd., United Kingdom, pp. 842-849.

Pierce, B.N., Clarke, I.J., Turner, A.I., Rivalland, E.T.A., Tilbrook, A.J., 2008, Cortisol disrupts the ability of estradiol-17{beta} to induce the LH surge in ovariectomized ewes, Domestic Animal Endocrinology, vol 0, Elsevier Inc., United States, p. 0.

Smith, J.T., Rao, A., Pereira, A., Caraty, A., Millar, R., Clarke, I.J., 2008, Kisspeptin is present in ovine hypophysial portal blood but does not increase during the preovulatory luteinizing hormone surge: Evidence that gonadotropes are not direct targets of kisspeptin in vivo, Endocrinology [P], vol 149, issue 4, The Endocrine Society, USA, pp. 1951-1959.

Clarke, I.J., Puspita Sari, I., Qi, Y., Smith, J.T., Parkington, H.C., Ubuka, T., Iqbal, J., Li, Q., Tilbrook, A.J., Morgan, K., Pawson, A.J., Tsutsui, K., Millar, R., Bentley, G.E., 2008, Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion, Endocrinology, vol 149, issue 11, The Endocrine Society, United States, pp. 5811-5821.

Henry, B.A., Dunshea, F.R., Gould, M., Clarke, I.J., 2008, Profiling postprandial thermogenesis in muscle and fat of sheep and the central effect of leptin administration, Endocrinology [P], vol 149, issue 4, The Endocrine Society, USA, pp. 2019-2026.

Pierce, B.N., Hemsworth, P.H., Rivalland, E.T.A., Wagenmaker, E.R., Morrissey, A.D., Papargiris, M., Clarke, I.J., Karsch, F.J., Turner, A.I., Tilbrook, A.J., 2008, Psychosocial stress suppresses attractivity, proceptivity and pulsatile LH secretion in the ewe, Hormones and Behavior, vol 54, issue 3, Elsevier Inc (Academic Press), USA, pp. 424-434.

Wagner, G.C., Johnston, J.D., Clarke, I.J., Lincoln, G.A., Hazlerigg, D.G., 2008, Redefining the limits of day length responsiveness in a seasonal mammal, Endocrinology [P], vol 149, issue 1, The Endocrine Society, USA, pp. 32-39.

Tilbrook, A.J., Rivalland, E.T.A., Turner, A.I., Lambert, G.W., Clarke, I.J., 2008, Responses of the hypothalamopituitary adrenal axis and the sympathoadrenal system to isolation/restraint stress in sheep of different adiposity, Neuroendocrinology, vol 87, issue 4, S. Karger AG, Switzerland, pp. 193-205.

Scott, C.J., Clarke, I.J., Tilbrook, A.J., 2008, The effect of testosterone and season on prodynorphin messenger RNA expression in the preoptic area-hypothalamus of the ram, Domestic Animal Endocrinology, vol 34, issue 4, Elsevier Inc., United States, pp. 440-450.

Smith, J.T., Coolen, L.M., Kriegsfeld, L.J., Puspita Sari, I., Jaafarzadehshirazi, M.R., Maltby, M., Bateman, K., Goodman, R.L., Tilbrook, A.J., Ubuka, T., Bentley, G.E., Clarke, I.J., Lehman, M.N., 2008, Variation in kisspeptin and RFamide-Related Peptide (RFRP) expression and terminal connections to gonadotropin-releasing hormone neurons in the brain: A novel medium for seasonal breeding in the sheep, Endocrinology, vol 149, issue 11, The Endocrine Society, United States, pp. 5770-5782.

Szymanski, L.A., Schneider, J.E., Friedman, M.I., Ji, H., Kurose, Y., Blache, D., Rao, A., Dunshea, F.R., Clarke, I.J., 2007, Changes in insulin, glucose and ketone bodies, but not leptin or body fat content precede restoration of luteinising hormone secretion in ewes, Journal of Neuroendocrinology [P], vol 19, issue 6, Wiley-Blackwell Publishing Ltd, UK, The Netherlands & USA, pp. 449-460.

Anukulkitch, C., Rao, A., Dunshea, F.R., Blache, D., Lincoln, G.A., Clarke, I.J., 2007, Influence of photoperiod and gonadal status on food intake, adiposity, and gene expression of hypothalamic appetite regulators in a seasonal mammal, American Journal Of Physiology-Regulatory Integrat..., vol 292, issue 1, American Physiological Society, USA, pp. R242-R252.

Rivalland, E.T.A., Clarke, I.J., Turner, A.I., Pompolo, S., Tilbrook, A.J., 2007, Isolation and restraint stress results in differential activation of corticotrophin-releasing hormone and arginine vasopressin neurons in sheep, Neuroscience, vol 145, issue 3, Pergamon-Elsevier Science Ltd, Oxford England UK, pp. 1048-1058.

Smith, J.T., Clay, C., Caraty, A., Clarke, I.J., 2007, KiSS-1 messenger ribonucleic acid expression in the hypothalamus of the ewe is regulated by sex steroids and season, Endocrinology, vol 148, The Endocrine Society, USA, pp. 1150-1157.

Smith, J.T., Clarke, I.J., 2007, Kisspeptin expression in the brain: Catalyst for the initiation of puberty, Reviews in Endocrine & Metabolic Disorders, vol 8, issue 1, Springer, Dordrecht Netherlands, pp. 1-9.

Goodman, R.L., Lehman, M.N., Smith, J.T., Coolen, L.M., de Oliveira, C.V., Jafarzadehshirazi, M.R., Pereira, A., Iqbal, J., Caraty, A., Ciofi, P., Clarke, I.J., 2007, Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B, Endocrinology, vol 148, issue 12, Endocrine Society, USA, pp. 5752-5760.

Caraty, A., Smith, J.T., Lomet, D., Ben Said, S., Morrissey, A., Cognie, J., Doughton, B.W., Baril, G., Briant, C., Clarke, I.J., 2007, Kisspeptin synchronizes preovulatory surges in cyclical ewes and causes ovulation in seasonally acyclic ewes, Endocrinology, vol 148, issue 11, Endocrine Society, Chevy Chase MD USA, pp. 5258-5267.

Qi, Y., Iqbal, J., Oldfield, B.J., Clarke, I.J., 2007, Neural connectivity in the mediobasal hypothalamus of the sheep brain, Neuroendocrinology, vol 87, Karger, Basel, Switzerland, pp. 91-112.

Iqbal, J., Latchoumanin, O.A.L., Clarke, I.J., 2007, Rapid in vivo effects of estradiol-17beta in ovine pituitary gonadotropes are displayed by phosphorylation of extracellularly regulated kinase, serine/threonine kinase, and 3',5'-cyclic adenosine 5'-monophosphate-responsive element-binding protein, Endocrinology [P], vol 148, issue 12, The Endocrine Society, USA, pp. 5794-5802.

Tilbrook, A.J., Turner, A.I., Ibbott, M.D., Clarke, I.J., 2006, Activation of the hypothalamo-pituitary-adrenal axis by isolation and restraint stress during lactation in ewes: effect of the presence of the lamb and suckling, Endocrinology, vol 147, issue 7, The Endocrine Society, USA, pp. 3501-3509.

Lincoln, G.A., Clarke, I.J., Hut, R.A., Hazlerigg, D.G., 2006, Characterizing a Mammalian Circannual Pacemaker, Science, vol 314, issue 5807, American Association for the Advancement of Science, Washington USA, pp. 1941-1944.

Pompolo, S., Pereira, A.M., Estrada, K., Clarke, I.J., 2006, Colocalization of Kisspeptin and Gonadotropin-Releasing Hormone in the Ovine Brain, Endocrinology, vol 147, issue 2, The Endocrine Society, USA, pp. 804-810.

Iqbal, J., Kurose, Y., Canny, B.J., Clarke, I.J., 2006, Effects of central infusion of ghrelin on food intake and plasma levels of growth hormone, luteinizing hormone, prolactin, and cortisol secretion in sheep, Endocrinology, vol 147, issue 1, The Endocrine Society, Chevy Chase USA, pp. 510-519.

Estrada, K., Clay, C., Pompolo, S., Smith, J.T., Clarke, I.J., 2006, Elevated KiSS-1 expression in the arcuate nucleus prior to the cyclic preovulatory gonadotrophin-releasing hormone/lutenising hormone surge in the ewe suggests a stimulatory role for kisspeptin in oestrogen-positive feedback, Journal of Neuroendocrinology, vol 18, issue 10, Blackwell Publishing, Oxford England, pp. 806-809.

Pogoda, P., Egermann, M., Schnell, J.C., Priemel, M., Schilling, A.F., Alini, M., Schinke, T., Rueger, J.M., Schneider, E., Clarke, I.J., Amling, M., 2006, Leptin inhibits bone formation not only in rodents, but also in sheep, Journal of Bone and Mineral Research, vol 21, issue 10, American Society for Bone and Mineral Research, Washington USA, pp. 1591-1599.

Tilbrook, A.J., Clarke, I.J., 2006, Neuroendocrine mechanisms of innate states of attenuated responsiveness of the hypothalamo-pituitary adrenal axis to stress, Frontiers in Neuroendocrinology, vol 27, issue 3, Academic Press Inc Elsevier Science, San Diego USA, pp. 285-307.

Rivalland, E.T.A., Tilbrook, A.J., Turner, A.I., Iqbal, J., Pompolo, S., Clarke, I.J., 2006, Projections to the preoptic area from the paraventricular nucleus, arcuate nucleus and the bed nucleus of the stria terminalis are unlikely to be involved in stress-induced suppression of GnRH secretion in sheep, Neuroendocrinology, vol 84, issue 1, S Karger AG, Switzerland, pp. 1-13.

Stackpole, C.A., Clarke, I.J., Breen, K.M., Turner, A.I., Karsch, F.J., Tilbrook, A.J., 2006, Sex difference in the suppressive effect of Cortisol on pulsatile secretion of luteinizing hormone in sheep, Endocrinology, vol 147, issue 12, The Endocrine Society, USA, pp. 5921-5931.

Clarke, I.J., Scott, C.J., Pereira, A.M., Pompolo, S., 2006, The role of noradrenaline in the generation of the preovulatory LH surge in the ewe, Domestic Animal Endocrinology, vol 30, issue 4, Elsevier Science Inc, New York NY USA, pp. 260-275.

Phillips, D.J., Jones, K.L., Clarke, I.J., Scheerlinck, J.Y., de Kretser, D.M., 2005, Activin A: From sometime reproductive factor to genuine cytokine, Veterinary Immunology and Immunopathology [P], vol 108, issue 1-2, Elsevier BV, The Netherlands, pp. 23-27.

Kurose, Y., Iqbal, J., Rao, A., Murata, Y., Hasegawa, Y., Terashima, Y., Kojima, M., Kangawa, K., Clarke, I.J., 2005, Changes in expression of the genes for the leptin receptor and the growth hormone-releasing peptide/ghrelin receptor in the hypothalamic arcuate nucleus with long-term manipulation of adiposity by dietary means, Journal of Neuroendocrinology, vol 17, issue 6, Blackwell Publishing, Oxford England, pp. 331-340.

Rivalland, E.T.A., Iqbal, J., Clarke, I.J., Turner, A.I., Tilbrook, A.J., 2005, Co-localization and distribution of corticotrophin-releasing hormone, arginine vasopressin and enkephalin in the paraventricular nucleus of sheep: a sex comparison, Neuroscience, vol 132, issue 3, Elsevier Ltd, Oxford UK, pp. 755-766.

Clarke, I.J., Tobin, V.A., Pompolo, S., Pereira, A.M., 2005, Effects of changing gonadotropin-releasing hormone pulse frequency and estrogen treatment on levels of estradiol receptor-alpha and induction of Fos and phosphorylated cyclic adenosine monophosphate response element binding protein in pituitary [...], Endocrinology [P], vol 146, issue 3, The Endocrine Society, USA, pp. 1128-1137.

Pompolo, S., Ischenko, O., Pereira, A.M., Iqbal, J., Clarke, I.J., 2005, Evidence that projections from the bed nucleus of the stria terminalis and from the lateral and medial regions of the preoptic area provide input to gonadotropin releasing hormone (GNRH) neurons in the female sheep brain, Neuroscience [P], vol 132, issue 2, Pergamon, UK, France, pp. 421-436.

Anderson, S.T., Kusters, D.H., Clarke, I.J., Pow, D.V., Curlewis, J.D., 2005, Expression of pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1R) in the ewe hypothalamus: distribution and colocalization with tyrosine hydroxylase-immunoreactive neurones, Journal of Neuroendocrinology [P], vol 17, issue 5, Wiley-Blackwell Publishing Ltd, UK, The Netherlands, USA, pp. 298-305.

Iqbal, J., Manley, T.R., Yue, Q., Namavar, M.R., Clarke, I.J., 2005, Noradrenergic regulation of hypothalamic cells that produce growth hormone-releasing hormone and somatostatin and the effect of altered adiposity in sheep, Journal of Neuroendocrinology, vol 17, issue 6, Blackwell Publishing, Oxford England, pp. 341-352.

Dufourny, L., Caraty, A., Clarke, I.J., Robinson, J.E., Skinner, D.C., 2005, Progesterone-receptive beta-endorphin and dynorphin B neurons in the arcuate nucleus project to regions of high gonadotropin-releasing hormone neuron density in the ovine preoptic area: A retrograde labeling study, Neuroendocrinology [P], vol 81, issue 3, S. Karger AG, Switzerland, pp. 139-149.

Dufourny, L., Caraty, A., Clarke, I.J., Robinson, J.E., Skinner, D.C., 2005, Progesterone-receptive dopaminergic and neuropeptide Y neurons project from the arcuate nucleus to gonadotropin-releasing hormone-rich regions of the ovine preoptic area, Neuroendocrinology [P], vol 82, issue 1, S. Karger AG, Switzerland, pp. 21-31.

Iqbal, J., Manley, T.R., Ciofi, P., Clarke, I.J., 2005, Reduction in adiposity affects the extent of afferent projections to growth hormone-releasing hormone & somatostatin neurons & degree of colocalization of Neuropeptides in Growth Hormone-Releasing Hormone & Somatostatin Cells of Ovine Hypothalamus, Endocrinology, vol 146, issue 11, The Endocrine Society, Chevy Chase USA, pp. 4776-4785.

Broadbear, J.H., Pierce, B.N., Clarke, I.J., Canny, B.J., 2005, Role of sex and sex steroids in mediating pituitary-adrenal responses to acute buspirone treatment in sheep, Journal of Neuroendocrinology, vol 17, issue 12, Blackwell Publishing Ltd, UK, pp. 804-810.

Clarke, I.J., Pompolo, S., 2005, Synthesis and secretion of GnRH, Animal Reproduction Science [P], vol 88, issue 1-2, Elsevier BV, The Netherlands, pp. 29-55.

Clarke, I.J., Backholer, K., Tilbrook, A.J., 2005, Y2 receptor-selective agonist delays the estrogen-induced luteinizing hormone surge in ovariectomized Ewes, but Y1-receptor-selective agonist stimulates voluntary food intake, Endocrinology, vol 146, issue 2, The Endocrine Society, USA, pp. 769-775.

Broadbear, J.H., Nguyen, T., Clarke, I.J., Canny, B.J., 2004, Antidepressants, sex steroids and pituitary-adrenal response in sheep, Psychopharmacology, vol 175, issue 2, Springer-Verlag, New York USA, pp. 247-255.

Jones, K.L., de Kretser, D.M., Clarke, I.J., Scheerlinck, J., Phillips, D.J., 2004, Characterisation of the rapid release of activin A following acute lipopolysaccharide challenge in the ewe, Journal of Endocrinology, vol 182, issue 1, Society for Endocrinology, UK, pp. 69-80.

Breen, K.M., Stackpole, C.A., Clarke, I.J., Pytiak, A.V., Tilbrook, A.J., Wagenmaker, E.R., Young, E.A., Karsch, F.J., 2004, Does the type II glucocorticoid receptor mediate cortisol-induced suppression in pituitary responsiveness to gonadotropin-releasing hormone?, Endocrinology, vol 145, issue 6, The Endocrine Society, Bethesda USA, pp. 2739-2746.

Henry, B.A., Goding, J.W., Tilbrook, A.J., Dunshea, F.R., Blache, D., Clarke, I.J., 2004, Leptin-mediated effects of undernutrition or fasting on luteinizing hormone and growth hormone secretion in ovariectomized ewes depend on the duration of metabolic perturbation, Journal of Neuroendocrinology, vol 16, issue 3, Blackwell Publishing Ltd, UK, pp. 244-255.

Keenan, D.M., Alexander, S.F., Irvine, C.H.G., Clarke, I.J., Scott, C.J., Turner, A.I., Tilbrook, A.J., Canny, B.J., Veldhuis, J.D., 2004, Reconstruction of in vivo time-evolving neuroendocrine dose-response properties unveils admixed deterministic and stochastic elements, Proceedings of the National Academy of Sciences of the United States of America, vol 101, issue 17, National Academy of Sciences, USA, pp. 6740-6745.

Scott, C.J., Clarke, I.J., Tilbrook, A.J., 2004, Sex differences in the distribution and abundance of androgen receptor mRNA-containing cells in the preoptic area and hypothalamus of the ram and ewe, Journal of Neuroendocrinology, vol 16, issue 12, Blackwell Publishing Ltd, Oxford UK, pp. 956-963.

Broadbear, J.H., Hutton, L.C., Clarke, I.J., Canny, B.J., 2004, Sex differences in the pituitary-adrenal response following acute antidepressant treatment in sheep, Psychopharmacology, vol 171, Springer-Verlag, New York USA, pp. 450-457.

Clarke, I.J., Backholer, K., Tilbrook, A.J., 2004, Y2 receptor-selective agonist delays the estrogen-induced LH surge in overiectomised ewes but Y1-receptor-selective agonist stimulates voluntary food intake, Endocrinology, vol 146, issue 1, The Endocrine Society, Bethesda USA, pp. 769-775.

Scott, C.J., Mariani, M., Clarke, I.J., Tilbrook, A.J., 2003, Effect of testosterone and season on proenkephalin messenger RNA expression in the preoptic area of the hypothalamus in the ram, Biology of Reproduction, vol 69, issue 6, Society for the Study of Reproduction, Madison USA, pp. 2015-2021.

Pompolo, S., Pereira, A., Scott, C.J., Fujiyma, F., Clarke, I.J., 2003, Evidence for estrogenic regulation of gonadotropin-releasing hormone neurons by glutamatergic neurons in the ewe brain: an immunohistochemical study using an antibody against vesicular glutamate transporter-2, The Journal of Comparative Neurology, vol 465, issue 1, Wiley-Liss, New York USA, pp. 136-144.

Iqbal, J., Henry, B.A., Pompolo, S., Rao, A., Clarke, I.J., 2003, Long-term alteration in bodyweight and food restriction does not affect the gene expression of either preproorexin or prodynorphin in the sheep, Neuroscience [P], vol 118, issue 1, Pergamon, UK, France, pp. 217-226.

Scott, C.J., Clarke, I.J., Tilbrook, A.J., 2003, Neuronal inputs from the hypothalamus and brain stem to the medial preoptic area of the ram: neurochemical correlates and comparison to the ewe, Biology of Reproduction, vol 68, issue 4, Society for the Study of Reproduction, Madison USA, pp. 1119-1133.

Estrada, K.M., Pompolo, S., Morris, M.J., Tilbrook, A.J., Clarke, I.J., 2003, Neuropeptide Y (NPY) delays the oestrogen-induced luteinizing hormone (LH) surge in the ovariectomized ewe: further evidence that NPY has a predominant negative effect on the LH secretion in the ewe, Journal of Neuroendocrinology, vol 15, issue 11, Blackwell Publishing Ltd, Oxford UK, pp. 1011-1020.

Clarke, I.J., Rao, A., Chilliard, Y., Delavaud, C., Lincoln, G.A., 2003, Photoperiod effects on gene expression for hypothalamic appetite-regulating peptides and food intake in the ram, American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol 284, issue 1, American Physiological Society, Bethesda USA, pp. 101-115.

Lincoln, G.A., Andersson, H., Clarke, I.J., 2003, Prolactin cycles in sheep under constant photoperiod: Evidence that photorefractoriness develops within the pituitary gland independently of the prolactin output signal, Biology Of Reproduction [P], vol 69, issue 4, Society for the Study of Reproduction, USA, pp. 1416-1423.

Pompolo, S., Pereira, A.M., Kaneko, T., Clarke, I.J., 2003, Seasonal changes in the inputs to gonadotropin-releasing hormone neurones in the ewe brain: An assessment by conventional fluorescence and confocal microscopy, Journal of Neuroendocrinology [P], vol 15, issue 5, Wiley-Blackwell Publishing Ltd, UK, The Netherlands, USA, pp. 538-545.

Stackpole, C.A., Turner, A.I., Clarke, I.J., Lambert, G.W., Tilbrook, A.J., 2003, Seasonal differences in the effect of isolation and restraint stress on the luteinizing hormone response to gonadotropin-releasing hormone in hypothalamopituitary disconnected, gonadectomized rams and ewes, Biology of Reproduction, vol 69, issue 4, Society for the Study of Reproduction, Madison Wisconsin USA, pp. 1158-1164.

Turner, A.I., Canny, B., Hobbs, R.J., Bond, J.D., Clarke, I.J., Tilbrook, A., 2002, Influence of sex and gonadal status of sheep on cortisol secretion in response to ACTH and on cortisol and LH secretion in response to stress: importance of different stressors, Journal of Endocrinology, vol 173, issue 1, Society for Endocrinology, Bristol England, pp. 113-122.

Clarke, I.J., Moore, L.G., Veldhuis, J., 2002, Intensive direct cavernous sinus sampling identifies high-frequency, nearly random patterns of FSH secretion in ovariectomized ewes: combined appraisal by RIA and bioassay, Endocrinology, vol 143, issue 1, Endocrine Society, Chevy Chase, MD, USA, pp. 117-129.

Turner, A.I., Revilland, E.T., Clarke, I.J., Lambert, G.W., Morris, M.J., Tilbrook, A., 2002, Noradrenaline, but not Neuropeptide Y, is elevated in cerebrospinal fluid from the third cerebral ventricle following audiovisual stress in gonadectomised rams and ewes, Neuroendocrinology, vol 76, issue 6, Karger, Basel Switzerland, pp. 373-380.

Tilbrook, A., Turner, A.I., Clarke, I.J., 2002, Stress and Reproduction: Central Mechanisms and Sex Differences in Non-rodent Species, Stress, vol 5, issue 2, Taylor & Francis Health Sciences, Berkeshire UK, pp. 83-100.

Clarke, I.J., Pompolo, S., Scott, C.J., Rawson, J., Caddy, D.J., Jakubowska, A.E., Pereira, A.M., 2001, Cells of the arcuate nucleus and ventromedial nucleus of the ovariectomized ewe that respond to oestrogen: A study using fos immunohistochemistry, Journal of Neuroendocrinology, vol 13, issue 11, Blackwell Science Ltd, Oxofrd England, pp. 934-941.

Scott, C.J., Pereira, A.M., Tilbrook, A., Rawson, J., Clarke, I.J., 2001, Changes in preoptic and hypothalamic levels of progesterone receptor mRNA across the oestrous cycle of the ewe, Journal of Neuroendocrinology, vol 13, issue 5, Blackwell Science Ltd, Oxford England, pp. 401-406.

Henry, B.A., Rao, A., Tilbrook, A., Clarke, I.J., 2001, Chronic food-restriction alters the expression of somatostatin and growth hormone-releasing hormone in the ovariectomised ewe, Journal of Endocrinology, vol 170, Society for Endocrinology, Stokebristol England, pp. R1-R5.

Henry, B.A., Rao, A., Ikenasio, B., Mountjoy, K., Tilbrook, A., Clarke, I.J., 2001, Differential expression of cocaine- and amphetamine-regulated transcript and agouti related-protein in chronically food-restricted sheep, Brain Research, vol 918, issue 1-2, Elsevier Science BV, Amsterdam Netherlands, pp. 40-50.

Iqbal, J., Pompolo, S., Sakurai, T., Clarke, I.J., 2001, Evidence that orexin-containing neurones provide direct input to gonadotropin-releasing hormone neurones in the ovine hypothalamus, Journal of Neuroendocrinology, vol 13, Blackwell Publishing, Oxford England, pp. 1033-1041.

Iqbal, J., Pompolo, S., Murakami, T., Grouzmann, E., Sakurai, T., Meister, B., Clarke, I.J., 2001, Immunohistochemical characterization of localization of long-form leptin receptor (Ob-Rb) in neurochemically defined cells in the ovine hypothalamus, Brain Research, vol 920, Elsevier Science BV, Amsterdam The Netherlands, pp. 55-64.

Tilbrook, A., de Kretser, D.M., Clarke, I.J., 2001, Influence of the degree of stimulation of the pituitary by gonadotrophin-releasing hormone on the action of inhibin and testosterone to suppress the secretion of the gonadotrophins in rams, Biology of Reproduction, vol 64, Society for the Study of Reproduction, Madison Wisconsin USA, pp. 473-481.

Henry, B.A., Goding, J., Tilbrook, A., Dunshea, F., Clarke, I.J., 2001, Intracerebroventricular infusion of leptin elevates the secretion of luteinising hormone without affecting food intake in long-term food-restricted sheep, but increases growth hormone irrespective of bodyweight, Journal of Endocrinology, vol 168, Society of Endocrinology, Bradley Stokebristol England, pp. 67-77.

Clarke, I.J., Henry, B.A., Iqbal, J., Goding, J., 2001, Leptin and the regulation of food intake and the neuroendocrine axis in sheep, Clinical and Experimental Pharmacology and Physiology, vol 28, issue 1-2, Blackwell Science Asia, Carlton Vic Australia, pp. 106-107.

Iqbal, J., Pompolo, S., Dumont, L.M., Wu, C., Mountjoy, K., Henry, B.A., Clarke, I.J., 2001, Long-term alterations in body weight do not affect the expression of melanocortin receptor-3 and -4 mRNA in the ovine hypothalamus, Neuroscience, vol 105, issue 4, Pergamon-Elsevier Science Ltd, Oxford England, pp. 931-940.

Tilbrook, A., Clarke, I.J., 2001, Negative feedback regulation of the secretion and actions of gonadotrophin-releasing hormone in males, Biology of Reproduction, vol 64, Society for the Study of Reproduction, Madison Wisconsin USA, pp. 735-742.

Rawson, J., Scott, C.J., Pereira, A.M., Jakubowska, A.E., Clarke, I.J., 2001, Noradrenergic projections from the A1 field to the preoptic area in the brain of the ewe and fos responses to oestrogen in the A1 cells, Journal of Neuroendocrinology, vol 13, issue 2, Blackwell Science Ltd, Oxford England, pp. 129-138.

Turner, A.I., Tilbrook, A., Clarke, I.J., Scott, C.J., 2001, Progesterone and testosterone in combination act in the hypothalamus of castrated rams to regulate the secretion of LH, Journal of Endocrinology, vol 169, Society for Endocrinology, Stokebristol England, pp. 291-298.

Pompolo, S., Rawson, J.A., Clarke, I.J., 2001, Projections from the arcuate/ventromedial region of the hypothalamus to the preoptic area and bed nucleus of stria terminalis in the brain of the ewe; lack of direct input to gonadotropin-releasing hormone neurons, Brain Research, vol 904, Elsevier Science BV, Amsterdam Netherlands, pp. 1-12.

Clarke, I.J., Tilbrook, A., Turner, A.I., Doughton, B.W., Goding, J., 2001, Sex, fat and the tilt of the earth: effects of sex and season on the feeding response to centrally administered leptin in sheep, Endocrinology, vol 142, issue 6, Endocrine Society, USA, pp. 2725-2728.

Tilbrook, A.J., Turner, A.I., Clarke, I.J., 2000, Effects of stress on reproduction in non-rodent mammals: the role of glucocorticoids and sex differences, Reviews of Reproduction, vol 5, Elsevier Science, Amsterdam Netherlands, pp. 105-113.

Scott, C.J., Tilbrook, A.J., Rawson, J.A., Clarke, I.J., 2000, Gonadal steroid receptors in the regulation of GnRH secretion in farm animals, Animal reproduction science, vol 60-61, Elsevier Science, Amsterdam Netherlands, pp. 313-326.

Iqbal, J., Pompolo, S., Considine, R.V., Clarke, I.J., 2000, Localization of Leptin Receptor-Like Immunoreactivity in the Corticotropes, Somatotropes, and Gonadotropes in the Ovine Anterior Pituitary, Endocrinology, vol 141, issue 4, The Endocrine Society, Chevy Chase USA, pp. 1515-1520.

Iqbal, J., Pompolo, S., Murakami, T., Clarke, I.J., 2000, Localization of long-form leptin receptor in the somatostatin-containing neurons in the sheep hypothalamus, Brain Research [P], vol 887, issue 1, Elsevier BV, The Netherlands, pp. 1-6.

Henry, B.A., Tilbrook, A.J., Dunshea, F.R., Rao, A., Blache, D., Martin, G.B., Clarke, I.J., 2000, Long-term alterations in adiposity affect the expression of melanin-concentrating hormone and enkephalin but not proopiomelanocortin in the hypothalamus of ovariectomized ewes, Endocrinology, vol 141, Endocrine Society, Bethesda MD USA, pp. 1506-1514.

Clarke, I.J., Scott, C.L., Rao, A., Pompolo, S., Barker-Gibb, M.L., 2000, Seasonal changes int he expression of neuropeptide Y and pro-opiomelanocortin mRNA in the arcuate necleus of the ovariectomized ewe: relationship to the seasonal appetite and breeding cycles, Journal of Neuroendocrinology, vol 12 issue 11, Blackwell Science Ltd, Onsey Mede England, pp. 1105-1111.

Scott, C.L., Tilbrook, A.J., Simmons, D.M., Rawson, J.A., Chu, S., Fuller, P.J., Ing, N.H., Clarke, I.J., 2000, The distribution of cells containing estrogen receptor-alpha (ERalpha) and ERBeta messenger ribonucleic acid in the preoptic area and hypothalamus of the sheep: comparison of males and females, Endocrinology, vol 141, Endocrine Society, Bethesda MS USA, pp. 2951-2962.

Scott, C.J., Pereira, A.M., Rawson, J.A., Simmons, D.M., Rossmanith, W.G., Ing, N.H., Clarke, I.J., 2000, The distribution of progesterone receptor immunoreactivity and mRNA in the preoptic area and hypothalamus of the ewe: upregulation of progesterone receptor mRNA in the mediobasal hypothalamus by oestrogen, Journal of Neuroendocrinology, vol 12 issue 6, Blackwell Science, Onsey Mede England, pp. 565-575.

Henry, B.A., Goding, J.W., Alexander, W., Tilbrook, A.J., Canny, B.J., Dunshea, F.R., Rao, A., Mansell, A., Clarke, I.J., 1999, Central Administration of Leptin to Ovariectomized Ewes Inhibits Food Intake without Affecting the Secretion of Hormones from the Pituitary Gland: Evidence for a Dissociation of Effects on Appetite and Neuroendocrine Function, Endocrinology, vol 140:3, Endocrine Society, Bethesda USA, pp. 1175-1182.

Tilbrook, A.J., Canny, B., Stewart, B.J., Serapiglia, M.D., Clarke, I.J., 1999, Central administration of corticotrophin releasing hormone but not arginine vasopressin stimulates the secretion of lutenizing hormone in rams in the presence and absence of testosterone, Journal of Endocrinology, vol 162, Society for Endocrinology, Bristol UK, pp. 301-311.

Henry, B.A., Goding, J.W., Alexander, W., Tilbrook, A.J., Canny, B., Dunshea, F.R., Rao, A., Mansell, A., Clarke, I.J., 1999, Central administration of leptin to ovariectomised ewes inhibits food intake without affecting the secretion of hormones from the pituitary gland: evidence for a dissociation of effects on appetite and neuroendocrine function, Endocrinology, vol 140, Endocrine Society, Bethesda USA, pp. 1175-1182.

Tilbrook, A.J., de Kretser, D.M., Clarke, I.J., 1999, Changes in the suppressive effects of recombinant inhibin A on FSH secretion in ram lambs during sexual maturation: evidence for alterations in the clearance rate of inhibin, Journal of Endocrinology, vol 161, Society for Endocrinology, Bristol UK, pp. 219-229.

Tilbrook, A.J., de Kretser, D.M., Clarke, I.J., 1999, Changes in the suppressive effects of recombinant inhibin A on FSH secretion in ram lambs during sexual maturation: evidence for alterations in the clearance rate of inhibin, Journal of Endocrinology, vol 161, Society for Endocrinology, Bradley Stoke UK, pp. 219-229.

Clarke, I.J., Scott, C.L., Pereira, A.M., Rawson, J.A., 1999, Levels of dopamine beta hydroxylase immunoreactivity in the preoptic hypothalamus of the ovariectomized ewe following injection of oestrogen: evidence for increased noradrenaline release around the time of the oestrogen-induced surge in luteinizing h, Journal of Neuroendocrinology, vol 11 issue 7, Blackwell Science Ltd, Osney Mead Oxford UK, pp. 503-512.

Scott, C.L., Rawson, J.A., Pereira, A.M., Clarke, I.J., 1999, Oestrogen receptors in the brainstem of the female sheep: relationship to noradrenergic cells and cells projecting to the medical preoptic area, Journal of Neuroendocrinology, vol 11 issue 10, Blackwell Science Ltd, Osney Mead Oxford UK, pp. 745-755.

Tilbrook, A.J., de Kretser, D.M., Clarke, I.J., 1999, Seasonal changes in the negative feedback regulation of the secretion of the gonadotrophins by testosterone and inhibin in rams, Journal of Endocrinology, vol 160, Society for Endocrinology, Bristol UK, pp. 155-167.

Tilbrook, A.J., Canny, B., Serapiglia, M.D., Ambrose, T.J., Clarke, I.J., 1999, Suppression of the secretion of luteinizing hormone due to isolation / restraint stress in gonadectomised rams and ewes is influenced by sex steroids, Journal of Endocrinology, vol 160, Society for Endocrinology, Bristol UK, pp. 469-481.

Canny, B., O'Farrell, K.A., Clarke, I.J., Tilbrook, A.J., 1999, The influence of sex and gonadectomy on the hypothalamo-pituitary-adrenal axis of the sheep, Journal of Endocrinology, vol 162, Society for Endocrinology, Bristol UK, pp. 215-225.

Canny, B., O'Farrell, K.A., Clarke, I.J., Tilbrook, A.J., 1998, Angiotensin II- and phorbol ester-induced steriodogenesis by ovine adrenocortical cells: effect of sex and the gonadal status of the donor animal, Clinical and Experimental Pharmacology and Physiology, vol 25, Blackwell Science, Carlton Vic Australia, pp. 401-404.

Walsh, J.P., Clarke, I.J., 1998, Blockade of the oestrogen-induced luteinizing hormone surge in ovariectomized ewes by a highly selective opioid receptor agonist: Evidence for site of action, Neuro Endorinonology, vol 67, Blackwell Science, UK, pp. 164-170.

Chen, C., Farnworth, P.G., Petersenn, S., Musgrave, I., Canny, B., Clarke, I.J., 1998, Growth hormone-releasing peptide (GHRP-2) does not act via the human growth hormone-releasing factor receptor in GC cells, Endocrine, vol 9 (1), Humana Press, Totowa NJ USA, pp. 71-77.

Clarke, I.J., Brown, B.W., Tran, V.V., Scott, C.L., Fry, R.C., Millar, R.P., Rao, A., 1998, Neonatal immunization against gonadotropin-releasing hormone (GnRH) results in diminished GnRH secretion in adulthood, Endocrinology, vol 139 (4), The Endocrine Society, Bethesda MD USA, pp. 2007-2014.

Walsh, J.P., Simmons, D.M., Clarke, I.J., 1998, Proopiomelanocortin mRNA levels in ovine hypothalamus are not reduced at the time of the preovulatory luteinising hormone surge, Journal of Neuroendocrinology, vol 10, Blackwell Science, UK, pp. 803-808.

Scott, C.L., Rawson, J.A., Pereira, A.M., Clarke, I.J., 1998, The distribution of estrogen receptors in the brainstem of female sheep, Neuroscience Letters, vol 241, Elsevier, Ireland, pp. 29-32.

Roh, S., Clarke, I.J., Xu, R., Goding, J.W., Loneragan, K., Chen, C., 1998, The in vitro effect of leptin on basal and growth hormone-releasing hormone-stimulated growth hormone secretion from the ovine pituitary gland, Neuroendocrinology, vol 68, S. Karger AG, Basel, pp. 361-364.

Marks, S., Moore, N.R., Ryley, N.G., Clarke, I.J., Pointon, J.J., Strauss, B.J.G., Hockaday, T.D., 1997, Measurement of liver fat by MRI and its reduction by dexfenfluramine in NIDDM, International Journal of Obesity, vol 21, Stockton Press, England UK, pp. 274-279.

Conference Proceedings

Henry, B.A., Tilbrook, A.J., Dunshea, F.R., Canny, B., Rao, A., Clarke, I.J., 1999, Acute fasting (24 hours) causes negative energy balance but does not alter the secretion of hormones from the pituitary gland in fat and thin sheep, The Endocrine Society of Australia Proceedings 1999, Melbourne VIC 26-29 September 1999, Endocrine Society of Australia, Adelaide SA Australia, p. 85.

Henry, B.A., Dunshea, F.R., Canny, B., Tilbrook, A.J., Rao, A., Clarke, I.J., 1999, Expression of appetite regulating peptides in the hypothalamus of fat and thin sheep in relation to endocrinology and metabolic parameters, Proceedings of the 81st Annual Meeting of the Endocrine Society, San Diego USA 12-15 June 1999, The Endocrine Society Press, Bethesda USA, p. 375.

Scott, C.L., Tilbrook, A.J., Simmons, D.M., Rawson, J.A., Chu, S., Fuller, P.J., Ing, N., Clarke, I.J., 1999, Sexually dimorphic distribution of oestrogen receptor-alpha (ER alpha) and oestrogen receptor beta (ER beta) mRNA in the ovine hypothalamus, The Endocrine Society of Australia Proceedings, Melbourne VIC 26-29 September 1999, Endocrine Society of Australia, Adelaide SA Australia, p. 80.

Turner, A.I., Canny, B., Bond, J.D., Clarke, I.J., Parr, R.A., Serapiglia, M.D., Tilbrook, A.J., 1999, The effects of sex and gonadal status on the cortisol response to insulin-induced hypoglycaemia in sheep, The Endocrine Society of Australia Proceedings 1999, Melbourne VIC 26-29 September 1999, Endocrine Society of Australia, Adelaide SA Australia, p. 75.

Clarke, I.J., Barker-Gibb, M.L., Scott, C.L., Rao, A., 1999, The seasonal appetite cycle in sheep relates to the expression of neuropeptide Y (NPY) in the arcuate nucleus but not to the expression of pro-opiomelanocortin (POMC), Society for Neuroscience Abstracts, Miami Beach USA 23-28 October 1999, Society for Neuroscience, Washington DC USA, p. 1555.

Scott, C.L., Pereira, A.M., Rawson, J.A., Clarke, I.J., 1998, Estrogen receptor -a(ER) immunoreceptive(-ir) cells in the A1 region of the sheep brain stem project to the preoptic area(POA), Australian Society for Reproductive Biology, Perth WA 23-26 August 1998, University of Western Australia, Perth WA Australia, p. 55.

Henry, B.A., Goding, J.W., Alexander, W., Tilbrook, A.J., Canny, B., Clarke, I.J., 1998, High doses of leptin can reduce food intake in sheep whilst not affecting the secretion of pituitary hormones, Proceedings of the Endocrine Society, New Orleans Louisiana USA 24-27 June 1998, The Endocrine Society, Bethesda USA, pp. 101-102.

Tilbrook, A.J., Clarke, I.J., 1998, Ovulation is timed by the brain, Hormones and Women's Health: The Reproductive Years, Clayton Victoria 15-16 October 1998, Prince Henry's Institute of Medical Research, Melbourne Vic Australia, p. 14.

Henry, B.A., Goding, J.W., Alexander, W., Tilbrook, A.J., Canny, B., Dunshea, F.R., Rao, A., Clarke, I.J., 1998, The effect of leptin on food consumption and the secretion of pituitary hormones can be dissociated in the sheep, Proceedings of the 41st Annual Scientific Meeting of the Endocrine Society of Australia, Perth WA 25-27 August 1998, Endocrine Society of Australia, Melbourne Vic Australia, p. 75.

Scott, C.L., Pereira, A.M., Simmons, D., Ing, N., Rawson, J.A., Clarke, I.J., 1997, Distribution of estrogen receptor and progesterone receptor immunoreactivity and mRNA in sheep hypothalamus and brainstem, Society for Neurosciences 27th Annual Meeting, New Orleans USA,25-30 October 1997, Society for Neuroscience, Washington DC USA, p. 1505.

Tilbrook, A.J., de Kretser, D.M., Clarke, I.J., 1997, Negative feedback regulation of FSH secretion by inhibin in pre-pubertal rams, Biology of Reproduction, Portland, Oregon USA, 02/08/97 - 05/08/97, Biology of Reproduction, Portland Oregon USA, p. 170.

Scott, C.L., Pereira, A.M., Simmons, D., Rawson, J.A., Ing, N., Clarke, I.J., 1997, The distribution of oestrogen receptor (ER) immunoreactivity (-ir) and mRNA in the sheep hypothalamus and brainstem, Australian Society for Reproductive Biology Program annd Mini posters or Abstracts, Canberra,29Sept-1Oct 1997, Australia Society for Reproductive Biology, Canberra ACT Australia, p. 30.

Scott, C.L., Pereira, A.M., Simmons, D., Rawson, J.A., Ing, N., Clarke, I.J., 1997, The distribution of progesterone receptor (ER) immunoreactivity (-ir) and mRNA in the sheep hypothalamus and brainstem, The Endocrine Society of Australia Proceedings, Bondi Beach NSW,28Sept-2Oct 1997, Endocrine Society of Australia, Australia, p. 55.

Other

Boyle, J., Brennan, L., Brinkworth, G., Brown, W., Burger, H., Clarke, I., Corbould, A., Costello, M., Cussons, A., Davies, M., Deeks, A., Eden, J., Frearson, M., Hart, R., Hickey, T., Johnstone, P., Kidson, W., Knight, R., Lim, E., Lombard, C., Marsh, K., McAllister, V., Michelmore, J., Moran, L., Noakes, M., Norman, R., Rodgers, R., Rogers, P., Rombauts, L., Sloboda, D., Stepto, N., Stuckey, B., Talbot, M., Teede, H., Vollenhoven, B., Wong, J., 2011, Evidence-based guideline for the assessment and management of polycystic ovary syndrome A single, The Jean Hailes Foundation, Australia, pp. 1-132.

Yasin, S., Piterman, L., Clarke, I.J., 1997, Geriatrics Audit Workshop, 10th Annual Postgraduate Medical Refresher Course, Noosa - Conference Workshop.

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Characterising the link between cortisol, cortisol responsiveness and obesity.
Supervisors:
Henry, B (Main), Clarke, I (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Stress responsiveness as a marker of obesity predisposition.
Supervisors:
Clarke, I (Joint-co), Henry, B (Joint).

Completed Supervision

Student:
Anukulkitch, C.
Program of Study:
. 2004.
Supervisors:
Clarke, I (Main).
Student:
Anukulkitch, C.
Program of Study:
Influence of photoperiod, sex steroids, genetic selection and intrauterine growth restriction on gene expression for appetite regulating peptides in the hypothalamus of a seasonal mammal. (PHD) 2009.
Supervisors:
Clarke, I (Main).
Student:
Backholer, K.
Program of Study:
The role of the melanocortin system in the control of reproduction in the ewe. (PHD) 2009.
Supervisors:
Clarke, I (Main).
Student:
Clarke, S.
Program of Study:
The effects of sex steroids on energy balance in sheep. (PHD) 2012.
Supervisors:
Clarke, I (Main), Henry, B (Associate).
Student:
Estrada, K.
Program of Study:
Neuropeptidergic control of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) secretion throughout the estrous cycle of the ewe. (PHD) 2006.
Supervisors:
Clarke, I (Main), Tilbrook, A (Associate).
Student:
Henry, B.
Program of Study:
THE NEUROENDOCRINOLOGY OF BODYWEIGHT IN SHEEP: THE ROLE OF LEPTIN AND APPETITE REGULATING PEPTIDES IN THE HYPOTHALAMUS. (PHD) 2001.
Supervisors:
Clarke, I (Main), Tilbrook, A (Associate).
Student:
Papargiris, M.
Program of Study:
Mechanisms and mediators involved in regulating reproduction during stress in ewes. (PHD) 2010.
Supervisors:
Tilbrook, A (Main), Clarke, I (Associate).
Student:
Pierce, B.
Program of Study:
The effects of stress-like levels of cortisol on reproductive neuroendocrine function and sexual behavior in ewes. (PHD) 2008.
Supervisors:
Tilbrook, A (Main), Clarke, I (Associate).
Student:
Puspita Sari, I.
Program of Study:
Studies on the role of gonadotropin-inhibitory hormone (GnIH) in the neuroendocrine regulation of reproduction in the sheep. (PHD) 2010.
Supervisors:
Clarke, I (Main), Tilbrook, A (Associate).
Student:
Qi, Y.
Program of Study:
A study of neural pathways in the ovine hypothalamus that control food intake and energy expenditure. (PHD) 2009.
Supervisors:
Clarke, I (Main), Oldfield, B (Associate).
Student:
Rivalland, E.
Program of Study:
Central pathways activated during during stress that may modulate reproduction in sheep: a sex comparison. (PHD) 2005.
Supervisors:
Tilbrook, A (Main), Turner, A (Associate), Clarke, I (Associate).
Student:
Stackpole, C.
Program of Study:
THE EFFECTS OF ISOLATION AND RESTRAINT STRESS, AND CORTISOL, ON THE RESPONSIVENESS OF THE ANTERIOR PITUITARY TO GONADOTROPHIN-RELEASING HORMONE IN RAMS AND EWES. (PHD) 2004.
Supervisors:
Tilbrook, A (Main), Turner, A (Associate), Clarke, I (Associate).