G0G1

S

G2

M

Control of Secretion

GHIH (or)

SST (somatostatin)

(-)

Anterior Pituitary:

Hypothalamus: GHRH

(+)

GH(somatotropin)

Liver: IGF (somatomedins)

(+)

(-)

GROWTH HORMONE

direct effectsindirect effects

lipolysis in fat cells

+

carbohydratemetabolism

+

Insulin-like Growth Factor

+

fat cells muscle

chondrocytes

Protein synthesis

cartilage formation

lipogenesis

Increases FFA, glycerol, and sugars in circulation

BrainPituitary

Liver

IGF

IGF binding proteins (IGFBPs)

Growth

Growth Hormone (GH)

GH/IGF/IGFBP Axis

Insulin-like Growth Factor Binding Proteins (IGFBPs)

IGFBPs bind circulating IGF with high affinity & specificity

Functions:1. act as carriers of IGF in plasma2. prolong the half-life of IGF in

circulation3. regulate IGF access to receptor in

extracellular fluid (!)

IGFBPs—two main types

1. IGFBP-3most abundant form of IGFBPmain carrier of IGF in circulationpromotes IGF mediated somatic growthhigh IGFBP-3 associated w/ growth stimulation

2. IGFBP-1typically present in small amountshigh IGFBP-1 associated w/ growth inhibition

IGFBP-3

IGF

IGF receptor

LIVER

Cell

Growth Functions

Growth Functions

Cell

IGF receptor

LIVER

IGFBP-1

IGF

Summary• Growth factors move cell from G0 to G1

– Initiate cell cycle

• Growth Hormone– Direct effects:

• Lipolysis• Carbohydrate metabolism• Increase IGF secretion from liver

– Indirect effects through IGF• Increase lipogenesis in fat cells• Increase protein synthesis in muscle• Increase cartilage formation and growth in bone

• IGFBPs– IGFBP3 enhances growth– IGFBP1 inhibits growth

Clinical Aspects

• Stress effects on Growth

• Overproduction of GH

• Underproduction of GH

• End-organ resistance

Maternal Effect: GC effect on Offspring

Japanese quail

From Hayward LS & Wingfield JC (2004) GCE 135:365-371Days after implantation

implantscontrols

Human Studies

1. low birth weight

2. slow weight gain

3. smaller head size

4. are delayed in their walking

5. reduced speech development

Direct Effect:Stress-induced dwarfism

brought into the hospital months later

BrainPituitary

Liver

IGF

IGF binding proteins (IGFBPs)

Growth

Growth Hormone (GH)

GH/IGF/IGFBP Axis

GCs

Effects of Cortisol on Plasma IGF

Cortisol ↓ plasma IGF levelsEffect takes 24 hours

Fro

m K

ajim

ura

et

al. (

20

03

) JO

E 1

78

:91

-99

control 2 g/g 10 g/g

Time (h)0 2 4 8 24P

lasm

a IG

F (n

g/m

l)

Effects of Cortisol on Plasma IGFBPs

↓ plasma IGFBP-3 levels

↑ plasma IGFBP-1 levels

Cortisol induces rapid changes in plasma IGFBPs

Fro

m K

ajim

ura

et

al. (

20

03

) JO

E 1

78

:91

-99

Tilapia

control 2 g/g 10 g/g

IGFBP-3

OD

U

Time (h)

OD

U

0 2 4 8 24

IGFBP-1

Clinical Aspects

• Stress Effects on Growth– GCs decrease growth– GCs can act through IGF or IGF binding

proteins

• Overproduction of GH

• Underproduction of GH

• End-organ resistance

Acromegaly-overproduction of GH -before puberty: gigantism (excessive growth of long bones) -in adults: causes excessive growth of cartilage-symptoms

Clinical Aspects

• Stress Effects on Growth– GCs decrease growth– GCs can act through IGF binding proteins

• Overproduction of GH– Acromegaly– gigantism

• Underproduction of GH– Hypo-pituitary dwarfism

• End-organ resistance

IGF levels

Clinical Aspects

• Overproduction of GH– Acromegaly– gigantism

• Underproduction of GH– hypopituitary dwarfism– Stress-induced dwarfism

• End-organ resistance

Laron’s Syndrome

• Defective GH receptor• recessive gene• Lethal in males

Clinical Aspects

• Overproduction of GH– Acromegaly– gigantism

• Underproduction of GH– Hypopituitary dwarfism – Stress-induced dwarfism

• End-organ resistance– Laron’s Syndrome

bGH in Dairy Cows?

Pygmies from Central Africa