Endocrine controls of eating: CCK, leptin, and ghrelin.

The peripheral physiological and central nervous mechanisms contributing to the control of eating present formidable challenges to experimental analysis. One of the most productive approaches to these challenges has been endocrinological. This review introduces the endocrine control of eating by considering three hormonal signals that have been hypothesized to control hunger or satiation, cholecystokinin CCK, leptin, and ghrelin. The roles of these molecules in humans and in rodents are considered against a set of criteria established in classical endocrinology for establishing physiological endocrine action. It is concluded that according to these criteria, CCK's satiating action in humans is the best-established physiological endocrine action. In contrast, support for endocrine actions of leptin in satiation and of ghrelin in hunger is incomplete, and areas urgently requiring further research are identified. Finally, a review of work on these three hormones suggests the utility of a new conceptual scheme for understanding the endocrine control of eating. This scheme distinguishes between endocrine, in which the stimuli for hormonal secretion and the effect of secretion on eating are tightly coupled, and endocrine effects, in which one or both of these links is uncoupled. The implications of this concept for research design and interpretation of data are discussed. A vast literature links endocrine systems to the control of eating behavior [Geary, N. Hunger and satiation. In: Martini, L., ed. Encyclopedia of endocrine diseases. San Diego, CA: Academic Press, 2004, in press.]. This is fortunate for ingestive science. Endocrinology is a well-developed discipline with an impressive armamentarium of intellectual and technical tools. In contrast, ingestive science, i.e., the study of eating, drinking, and drug use, is at a more rudimentary stage of development. My general thesis here is that the adaptation and application of some of the well-accepted intellectual tools of endocrinology is likely to accelerate progress in ingestive science. The organization of the review is threefold. First, the treatment of endocrine controls of eating is selective. Just three hormones, CCK, leptin, and ghrelin, are considered. It is not clear that these are the three most important endocrine controls of eating, but they are each certainly interesting candidates, and comparisons among them are instructive. Second, I argue for the utility of the application of classical endocrine criteria for the identification of physiological effects of hormones, as adapted to eating behavior. This is done by introducing these criteria, considering each hormone's status with respect to them, and identifying the areas where relevant evidence is currently available or is lacking. Third, I argue for the utility of making explicit the distinction between endocrine actions, in which the stimuli for hormonal secretion and the effect of secretion on eating are tightly coupled, and endocrine actions, in which these links are uncoupled. This concept is assembled inductively in the course of the review.