This document discusses the hormone ghrelin. It was discovered in 1999 by Masayasu Kojima and colleagues after discovering the growth hormone secretagogue receptor. Ghrelin is a 28 amino acid polypeptide hormone secreted by the stomach that stimulates appetite and the release of growth hormone. It binds to the GH-secretgogue receptor. Ghrelin levels increase before meals and decrease after eating, influenced by factors like food intake, glucose, lipids, and insulin. Physiologically, ghrelin stimulates growth hormone secretion, increases appetite by acting on the hypothalamus, and increases gastric acid secretion and motility. Potential clinical applications of ghrelin are also mentioned.

1. In the name of god
Ghrelin hormone
Navab Ahmadi

2. 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)

3. 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

4. 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.

5. 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

6. 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)

7. 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

8. 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)

12. Effects of ghrelin

13. Other effects of ghrelin
 Inhibit proinflammatory cytokin (IL-1, IL-6, TNF)
 Increase bone mineral density
 Decrease MAP by decreasing peripheral vascular resistance

14. Possible clinical application of ghrelin

15. Thank you
Navab Ahmadi