In the name of god

Ghrelin hormone

Navab Ahmadi

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)

Effects of ghrelin

Other effects of ghrelin

Inhibit proinflammatory cytokin (IL-1, IL-6, TNF)

Increase bone mineral density

Decrease MAP by decreasing peripheral vascular resistance

Possible clinical application of ghrelin

Thank you

Navab Ahmadi