ghrelin hormone
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History of ghrelin
The discovery of ghrelin followed after the discovery of the growth
hormone secretagogue type 1A receptor in 1996 and was reported
by Masayasu Kojima and colleagues(Matsuyama) in 1999
The name is based on its role as a growth hormone-releasing
peptide, with reference to the Proto-Indo-European root ghre,
meaning to grow.(Growth Hormone Release Inducing = Ghrelin)
Introduction1
Ghrelin has emerged as the first identified circulating hunger hormone
Ghrelin is both a hormone in the endocrine system and a neurotransmitter in the nervous system
28 amino-acid polypeptide
Secreted by oxyntic cell in gastric fundus
Can be found in pancrease, intestine, hypothalamus, pituitary gland
Introduction2
Ghrelin is produced mainly by P/D1 cells, lining the fundus of the human stomach,
that contain granules filled with ghrelin
Also by epsilon cells of the pancreas that stimulates hunger
In rodents, X/A-like cells produce ghrelin.
Aside from the stomach and pancreas in adults, ghrelin cells are also found in the
duodenum, jejunum, i leum, and colon, with ghrelin concentration decreasing
from the duodenum to the colon.
Structure of ghrelin 28 amino acids
n-octanoyl contacts to third serine from N-terminal (important for hormone activity)
Bind to GH-secretgogue-receptor 1a (GHS-R1a)
G-protein coupled receptor
Factors influencing ghrelin secretion
Most important
Food intake
Ghrelin level increases 1-2 hr prior to meal, max just before eating and decreases dramatically within 1 hr after meal
Degree of ghrelin level decrease is in proportion with calories and composition of food (CHO can decrease ghrelin > fat)
Glucose, lipid, amino acid
Ghrelin ↓ in postprandial hypoglycemia or after administration of IV glucose/fat diet
High protein diet, essential amino acid →↑ ghrelin →↑ GH (controversial)
Factors influencing ghrelin secretion
↑ ghrelin
leptin
Fasting
GHRH, thyroid hormone
Testosterone
Sleep
Lean people/ low BMI
Anorexia nervosa
↓ ghrelin
Food intake
Glucose/lipid
Insulin
Somatostatin
PYY/PP
Obese people/high BMI
Physiological roles of ghrelin Hormonal effect
Stimulation of GH secretion
Synergistic of GHRH
↓ somatostatin secretion from hypothalamus
↑ ACTH, PRL, cortisol
Appetite
Acting at arcuate nucleus by stimulation of NPY/AGRP neurons
(neuropeptide Y/ Agouti-related peptide) →↑ appetite (orexigenic effect)
Gastric effects
↑ gastric acid secretion and motility (acting through vagus nerve which also has GHS-R1a receptor)
Other effects of ghrelin
Inhibit proinflammatory cytokin (IL-1, IL-6, TNF)
Increase bone mineral density
Decrease MAP by decreasing peripheral vascular resistance