Ghrelin: integrative neuroendocrine peptide in health and disease.
OBJECTIVE
Ghrelin is a novel gastric hormone recognized in 1999 as a mediator of growth hormone release. Since growth hormone is anabolic, an important function of ghrelin may be to coordinate energy needs with the growth process. Newly discovered biologic roles of ghrelin imply that it may have other important physiological functions as well. This is a review of recent clinically relevant, yet less well-known, physiologic actions of ghrelin.


BACKGROUND
Ghrelin has profound orexigenic, adipogenic, and somatotrophic properties, increasing food intake and body weight. Secreted predominantly from the stomach, ghrelin is the natural ligand for the growth hormone secretagogue receptor in the pituitary gland, thus fulfilling criteria of a brain-gut peptide. The brain-gut axis is the effector of anabolism by regulating growth, feeding, and metabolism via vagal afferents mediating ghrelin signaling. However, the wide tissue distribution of ghrelin suggests that it may have other functions as well.


METHODS
Systematic literature review of all PubMed citations between 1999 and August 2003 focusing on clinically relevant biochemical and physiological characteristics of ghrelin.


RESULTS
Ghrelin is an important component of an integrated regulatory system of growth and metabolism acting via the vagus nerve, and is implicated in a variety of altered energy states such as obesity, eating disorders, neoplasia, and cachexia. It also enhances immune responses and potentially down-regulates anti-inflammatory molecules. Ghrelin's role as a brain-gut peptide emphasizes the significance of afferent vagal fibers as a major pathway to the brain, serving the purpose of maintaining physiologic homeostasis.


CONCLUSIONS
The discovery of ghrelin has increased our understanding of feeding regulation, nutritional homeostasis, and metabolic processes. Further characterization of ghrelin's functions will likely generate new pharmacological approaches to diagnose and treat different disease entities including those related to the over-nutrition of obesity and the catabolic response to surgical trauma.
Wu
James T
JT
Department of Surgery, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA. jwu@downstate.edu
Kral
John G
JG
D001921:Brain / Q000502:physiology; D002100:Cachexia / Q000503:physiopathology; D002320:Cardiovascular Physiological Phenomena; D016638:Critical Illness; D004068:Digestive System Physiological Phenomena; D004734:Energy Metabolism / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology; D015390:Gastric Bypass; D054439:Ghrelin; D013006:Growth Hormone / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000503:physiopathology; D009479:Neuropeptides / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology; D036361:Peptide Hormones / Q000276:immunology / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D054440:Receptors, Ghrelin
D054439:Ghrelin; D009479:Neuropeptides; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013006:Growth Hormone