Growth hormone secretagogues: prospects and potential pitfalls.
The growth hormone secretagogues (GHSs) are the first well-characterised agents that rejuvenate the growth hormone (GH)/insulin-like growth factor (IGF-1) axis. This property was discovered during investigations of the underlying causative mechanisms of age-related endocrine changes. Chronic administration of the long acting GHS, MK-0677, reverses the age-related decline in pulse-amplitude of GH secretion and restores IGF-1 levels producing profiles typical of young adults. This restoration is accompanied by improvements in body composition in frail elderly subjects. When given acutely, the GHSs also increase appetite. Following cloning and characterisation of the GHS-receptor (GHS-R) an endogenous ligand, ghrelin, was isolated and identified. Ghrelin shares the GH releasing and orexigenic properties of the GHSs. Studies using Ghsr-null mice confirmed that the GHS-R was the ghrelin-receptor; hence, the GHSs should be considered to be 'ghrelin mimetics.' Ghrelin levels are reported to decline during ageing, therefore long-acting GHSs are ideal candidates for ghrelin replacement therapy.
Smith
Roy G
RG
Huffington Center on Aging and Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza N704, M320, Houston, TX 77030 3498, USA. rsmith@bcm.tmc.edu
Sun
Yuxiang
Y
Betancourt
Lorena
L
Asnicar
Mark
M
D000375:Aging; D000818:Animals; D001066:Appetite; D001921:Brain / Q000502:physiology; D054439:Ghrelin; D019382:Human Growth Hormone / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000737:chemistry / Q000502:physiology; D007109:Immunity; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000502:physiology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000502:physiology; D036361:Peptide Hormones / Q000008:administration & dosage / Q000009:adverse effects / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000502:physiology; D054440:Receptors, Ghrelin
D054439:Ghrelin; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I