Ghrelin: much more than a natural growth hormone secretagogue.
Ghrelin, a 28 amino acid acylated peptide predominantly produced by the stomach, displays strong growth hormone-releasing activity mediated by the hypothalamus-pituitary GH secretagogue receptors that were found to be specific for a family of synthetic, orally active GH secretagogues. The discovery of ghrelin brings us to a new understanding of the regulation of GH secretion. However, ghrelin is much more than simply a natural GH secretagogue. It also acts on other central and peripheral receptors and exhibits other actions, including stimulation of lactotroph and corticotroph secretion, orexigenic, influences gastroenteropancreatic functions, and has metabolic, cardiovascular and antiproliferative effects. Knowledge of the whole spectrum of biologic activities of this new hormone will provide new understanding of some critical aspects of neuroscience, metabolism and internal medicine. In fact, GHS were born more than 20 years ago as synthetic molecules, eliciting the hope that orally active GHS could be used to treat GH deficiency as an alternative to recombinant human GH. However, the dream did not become reality and the usefulness of GHS as an anabolic anti-aging intervention restoring the GH/IGF-I axis in somatopause is still unclear. Instead, we now face the theoretic possibility that GHS analogues acting as agonists or antagonists could become candidate drugs for the treatment of pathophysiologic conditions in internal medicine totally unrelated to disorders of GH secretion.
Broglio
Fabio
F
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy.
Arvat
Emanuela
E
Benso
Andrea
A
Gottero
Cristina
C
Prodam
Flavia
F
Granata
Riccarda
R
Papotti
Mauro
M
Muccioli
Giampiero
G
Deghenghi
Romano
R
Ghigo
Ezio
E
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D004703:Endocrine System / Q000502:physiology; D054439:Ghrelin; D049673:History, 20th Century; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D036361:Peptide Hormones; D010455:Peptides / Q000266:history / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D011388:Prolactin / Q000378:metabolism
D054439:Ghrelin; D036361:Peptide Hormones; D010455:Peptides; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin