Basic aspects of ghrelin action.
The identification of the natural ligand for growth hormone secretagogue receptor 1a (GHSR1a) added a new element to the complex machinery of the physiological regulators for both growth hormone (GH) secretion and food intake. Initially, the incorporation of this "novel system" contributes to clarify some aspects of the regulation of GH that previously were not fully understood. However, this system is not as simple as it was thought at first. Ghrelin and its receptor became recognized not only for stimulating GH release but also by the discovery that this system appeared to exert an important role on several aspects of energy homeostasis. In this way, GHSR1a becomes a potential therapeutic target for the treatment of wasting syndromes. One of the important features of GHSR1a is the basal activity in the absence of an agonist, resulting in a high degree of receptor internalization as well as of signaling activity. This constitutive activity seems to provide a tonic signal required for the development of normal height, probably through an effect on the GH axis. Additionally, GHSR1a might function as homo- or heteromeric complexes in living cells which introduce a key concept that could have significant implications in different aspects of receptor biogenesis and function. At molecular level, GHSR1a regulates the activation of the downstream mitogen-activated protein kinase, Akt, nitric oxide synthase, and AMPK cascades in different cellular systems. Added to this complexity, the idea that GHSR1a is not the single receptor for ghrelin has been progressively more recognized. In this sense, the available data are quite ambiguous and many fundamental questions need to be clarified. The purpose of this chapter is to summarize the most recent characteristics of GHSR1a as the features to define the action of ghrelin and its physiological implication.
Pazos
Yolanda
Y
Laboratory of Molecular Endocrinology, Research Area, Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela, Spain.
Casanueva
Felipe F
FF
Camiña
Jesus P
JP
D000818:Animals; D004734:Energy Metabolism; D054439:Ghrelin / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D051379:Mice; D051381:Rats; D054440:Receptors, Ghrelin / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D054439:Ghrelin; D054440:Receptors, Ghrelin; D013006:Growth Hormone