137 © The Authors Journal compilation © 2011 Biochemical Society Essays Biochem. (2011) 49, 137–151; doi:10.1042/BSE0480137 9 Mammalian clock output mechanisms Andries Kalsbeek 1 *†, Chun-Xia Yi*†, Cathy Cailotto‡, Susanne E. la Fleur*, Eric Fliers* and Ruud M. Buijs§ *Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands, †Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands, ‡Division of Gastroenterology and Hepatology, Academic Medical Center (AMC), Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands, and §Instituto de Investigaciones Biomedicas UNAM (Universidad Nacional Autónoma de Mexico), Ciudad Universitaria, Mexico City, DF 04510, Mexico Abstract In mammals many behaviours (e.g. sleep–wake, feeding) as well as physiological (e.g. body temperature, blood pressure) and endocrine (e.g. plasma corticosterone concentration) events display a 24 h rhythmicity. These 24 h rhythms are induced by a timing system that is composed of central and peripheral clocks. The highly co-ordinated output of the hypothalamic biological clock not only controls the daily rhythm in sleep–wake (or feeding– fasting) behaviour, but also exerts a direct control over many aspects of hormone release and energy metabolism. First, we present the anatomical connections used by the mammalian biological clock to enforce its endogenous rhythmicity on the rest of the body, especially the neuro-endocrine and energy homoeostatic systems. Subsequently, we review a number of physiological 1 To whom correspondence should be addressed (email a.kalsbeek@amc.uva.nl).