Ghrelin is a recently discovered stomach hormone that stimulates pituitary growth hormone (GH) secretion potently. The purpose of these experiments was to test the hypothesis that a stomach-ghrelin-pituitary-GH axis exists in which either an elevation or reduction in systemic GH levels will exert a negative or positive feedback action, respectively, on stomach ghrelin homeostasis. In rats, GH administration decreased stomach ghrelin mRNA levels and plasma ghrelin levels significantly. In GH-releasing hormone (GHRH) transgenic mice, GHRH overexpression decreased stomach ghrelin peptide levels when compared with control mice. In aged rats (25 months) stomach ghrelin mRNA and peptide levels and plasma ghrelin levels were decreased when compared with young rats (5 months). Because GH secretion is reduced in aged rats, the elevated stomach ghrelin production and secretion may reflect a decreased GH feedback on stomach ghrelin, homeostasis, and secretion. Together, these findings suggest that endogenous pituitary GH exerts a feedback action on stomach ghrelin homeostasis and support the hypothesis that a stomach-ghrelinpituitary GH axis exists.
KojimaM, HosodaH, MatsuoH, KangawaK. Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab12: 118122, 2001.
5.
WangG, LeeHM, EnglanderE, GreeleyGHJr.. Ghrelin: Not just another stomach hormone. Regul Pept105: 7581, 2002.
6.
TolleV, ZizzariP, TomasettoC, RioMC, EpelbaumJ, Bluet-PajotMT. In vivo and in vitro effects of ghrelin/motilin-related peptide on growth hormone secretion in the rat. Neuroendocrinology73: 5461, 2001.
7.
ArvatE, MaccarioM, Di VitoL, BroglioF, BensoA, GotteroC, PapottiM, MuccioliG, DieguezCEndocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: Comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone. J Clin Endocrinol Metab86: 11691174, 2001.
8.
SonntagWE, StegerRW, FormanLJ, MeitesJ. Decreased pulsatile release of growth hormone in old male rats. Endocrinology107: 18751879, 1980.
9.
FloriniJR, HarnedJA, RichmanRA, WeissJP. Effect of rat age on serum levels of growth hormone and somatomedins. Mech Ageing Dev15: 165176, 1981.
10.
LeeHM, WangG, EnglanderEW, KojimaM, GreeleyGHJr.. Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology143: 185190, 2002.
DebeljukL, WrightJC, PhelpsC, BartkeA. Transgenic mice overexpressing the growth-hormone-releasing hormone gene have high concentrations of tachykinins in the anterior pituitary gland. Neuroendocrinology70: 107116, 1999.
16.
HammerRE, BrinsterRL, RosenfeldMG, EvansRM, MayoKE. Expression of human growth hormone-releasing factor in transgenic mice results in increased somatic growth. Nature315: 413416, 1985.
17.
OsterMH, FielderPJ, LevinN, CroninMJ. Adaptation of the growth hormone and insulin-like growth factor-I axis to chronic and severe calorie or protein malnutrition. J Clin Invest95: 22582265, 1995.
18.
LeiliS, ScanesCG. The effects of protein restriction on insulin-like growth factor-I and IGF-binding proteins in chickens. Proc Soc Exp Biol Med218: 322328, 1998.
19.
NaganoM, ChastreE, ChoquetA, BaraJ, GespachC, KellyPA. Expression of prolactin and growth hormone receptor genes and their isoforms in the gastrointestinal tract. Am J Physiol268: G431G442, 1995.
20.
NewmanJB, LluisF, TownsendCMJr.. Somatostatin. In: ThompsonJC, GreeleyGHJr., RayfordPL, TownsendCMJr.., Eds. Gastrointestinal Endocrinology. New York: McGraw-Hill, p 286299, 1987.
21.
AsakawaA, InuiA, KagaT, YuzurihaH, NagataT, UenoN, MakinoS, FujimiyaM, NiijimaAGhrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology120: 337345, 2001.
22.
HorvathTL, DianoS, SotonyiP, HeimanM, TschopM. Minireview: Ghrelin and the regulation of energy balance: A hypothalamic perspective. Endocrinology142: 41634169, 2001.
23.
SeymourNE, AndersenDK. Pancreatic polypeptide and glucose metabolism. In: GreeleyGHJr.., Ed. Gastrointestinal Endocrinology. Totowa, NJ: Humana Press, pp 321334, 1999.
24.
WhitcombDC. Neuroendocrine control of the exocrine pancreas. In: GreeleyGHJr.., Ed. Gastrointestinal Endocrinology. Totowa, NJ: Humana Press, pp 243263, 1999.
25.
TannenbaumGS, EpelbaumJ, BowersCY. Interrelationship between the novel peptide ghrelin and somatostatin/growth hormone-releasing hormone in regulation of pulsatile growth hormone secretion. Endocrinology144: 967974, 2003.
