REVIEW ARTICLE Metabolic signals, hormones and neuropeptides involved in control of energy balance and reproductive success in hamsters* J. E. Schneider, 1 C. A. Buckley, 1 R. M. Blum, 1 D. Zhou, 1 L. Szymanski, 1 D. E. Day 2 and T. J. Bartness 2 1 Department of Biological Sciences, 111 Research Drive, Lehigh University, Bethlehem, PA 18015, USA 2 Department of Biology, Georgia State University, Atlanta, GA 30303, USA Keywords: estrous cycles, glucose, hamsters, hoarding, insulin, leptin Abstract In the `postgenome era', most research on the neuroendocrine control of energy homeostasis has focused on hormonal and neuropeptide control of food intake (i.e. the amount of food eaten) in rats and mice. The amount of food consumed is in¯uenced by both the motivation to procure food and the consummatory act of ingestion. In some species, the rate of food intake remains relatively constant, while survival is maintained via changes in food procurement, external storage and internal expenditure. For example, in hamsters, metabolic signals, peripheral hormones and central neuropeptides in¯uence hunger motivation, food hoarding and changes in energy expenditure without necessarily in¯uencing the amount of food ingested. A similar suite of metabolic signals, hormones and neuropeptides is involved in optimizing reproductive success under ¯uctuating energetic conditions. Reproductive processes are inhibited or delayed when energy expenditure outstrips energy intake and mobilization from storage. Estrous cyclicity in Syrian hamsters is sensitive to the availability of oxidizable glucose, but the presence of central glucose alone is not suf®cient for normal estrous cycles. Food deprivation-induced anestrus does not depend upon food deprivation-induced increases in concentrations of adrenal hormones such as glucocorticoids. If hormones such as insulin and leptin play a role, they might do so by modulating the availability of glucose detected at extra-hypothalamic sites, instead of or in addition to direct effects on the mechanisms that control gonadotropin releasing hormone secretion. Despite our ability to measure and manipulate gene transcription, understanding of fuel homeostasis requires examination of indirect effects of hormones and neuropeptides on peripheral metabolism, attention to the motivational as well as consummatory aspects of ingestion, and the study of behaviour in a natural or seminatural context. Energy homeostasis is accomplished by mechanisms that control food intake, energy expenditure and energy storage. A staggering number of central neuropeptides have been postulated as playing a role in energy homeostasis. Anabolic peptides such as neuropeptide Y (NPY) and agouti-related protein (AgRP) increase food intake and decrease energy expenditure, whereas catabolic peptides such as a-melanocortin-stimulating hormone (a-MSH) and cocaine- and amphetamine-regulated transcript (CART) have the opposite effects (reviewed by Elmquist et al., 1998, 1999; Schwartz et al., 2000). These central neural peptide systems can be directly controlled by primary metabolic stimuli, i.e. signals generated by increases and decreases in the availability of oxidizable metabolic fuels (reviewed by Friedman, 1998). In addition to these metabolic signals, peripheral hormones provide information about the availability of oxidizable and/or stored metabolic fuels. In rats and mice, food deprivation and concomitant decreases in the adipocyte hormone leptin and the pancreatic hormone insulin are associated with low levels of body fat, decreased energy expenditure and increased food intake. Treatment with these hormones modulates energy storage and expenditure and, in rodents, central treatment with either insulin or leptin decreases food intake (reviewed by Friedman & Halaas, 1998; Woods et al., 1998; Schneider & Watts, 2002). In other species, metabolic signals, peripheral hormones and central neuropeptides in¯uence food procurement behaviours without necessarily in¯uencing the amount of food ingested. For example, in Syrian hamsters, a period of food deprivation fails to in¯uence subsequent food intake. Hamsters rarely change meal size and frequency in response to a variety of stimuli that in¯uence these parameters in rats and mice (Silverman & Zucker, 1976; Schneider et al., 1988), and yet food deprivation increases hunger motivation in Syrian hamsters, as measured by the tendency to eat an unpalatable substance (Schneider et al., 1988). In nature, Syrian hamsters live in burrows where they are known to hoard large quantities of food. In the laboratory, when their nest boxes are connected to arti®cial burrows leading to an external food source, Syrian hamsters exhibit hoarding behaviour. After a period of food deprivation, Syrian hamsters show signi®cant increases in the amount of food hoarded (Lea & Tarpy, 1986), and treatment with leptin during food Correspondence: Dr Jill Ellen Schneider, as above. Email: Js0v@lehigh.edu *Presented at the workshop sponsored by the Serono Foundation on `The Neuroendocrine±Behaviour Interface in the Post-Genome Era', 31 August ± 1 September, Bristol, UK. Received 6 April 2002, revised 6 June 2002, accepted 7 June 2002 doi:10.1046/j.1460-9568.2002.02118.x European Journal of Neuroscience, Vol. 16, pp. 377±379, 2002 ã Federation of European Neuroscience Societies