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S. G 1. G 2. G 0. M. GHIH (or) SST (somatostatin). Hypothalamus:. GHRH. (+). (+). (-). GH (somatotropin). Anterior Pituitary:. (-). Liver:. IGF (somatomedins). Control of Secretion. indirect effects. direct effects. +. +. +. Insulin-like Growth Factor. carbohydrate

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Presentation Transcript
slide1

S

G1

G2

G0

M

control of secretion

GHIH (or)

SST (somatostatin)

Hypothalamus:

GHRH

(+)

(+)

(-)

GH

(somatotropin)

Anterior Pituitary:

(-)

Liver:

IGF (somatomedins)

Control of Secretion
slide3

indirect effects

direct effects

+

+

+

Insulin-like Growth Factor

carbohydrate

metabolism

lipolysis in fat cells

fat cells

muscle

Increases FFA, glycerol, and sugars in circulation

chondrocytes

Protein synthesis

lipogenesis

cartilage formation

GROWTH HORMONE

gh igf igfbp axis

IGF binding proteins (IGFBPs)

GH/IGF/IGFBP Axis

Brain

Pituitary

Growth Hormone (GH)

Liver

Growth

IGF

insulin like growth factor binding proteins igfbps
Insulin-like Growth Factor Binding Proteins (IGFBPs)
  • IGFBPs bind circulating IGF with high affinity & specificity
  • Functions:
    • act as carriers of IGF in plasma
    • prolong the half-life of IGF in circulation
    • regulate IGF access to receptor in extracellular fluid (!)
igfbps two main types
IGFBPs—two main types
  • IGFBP-3
    • most abundant form of IGFBP
    • main carrier of IGF in circulation
    • promotes IGF mediated somatic growth
    • high IGFBP-3 associated w/ growth stimulation
  • IGFBP-1
    • typically present in small amounts
    • high IGFBP-1 associated w/ growth inhibition
slide7

LIVER

IGF

IGFBP-3

Cell

IGF receptor

Growth Functions

slide8

LIVER

IGF

IGFBP-1

Cell

IGF receptor

Growth Functions

summary
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
Clinical Aspects
  • Stress effects on Growth
  • Overproduction of GH
  • Underproduction of GH
  • End-organ resistance
maternal effect gc effect on offspring

implants

controls

Days after implantation

Maternal Effect: GC effect on Offspring

Japanese quail

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

human studies
Human Studies
  • low birth weight
  • slow weight gain
  • smaller head size
  • are delayed in their walking
  • reduced speech development
gh igf igfbp axis14

IGF binding proteins (IGFBPs)

GH/IGF/IGFBP Axis

GCs

Brain

Pituitary

Growth Hormone (GH)

Liver

Growth

IGF

effects of cortisol on plasma igf

2 mg/g

10 mg/g

control

Plasma IGF (ng/ml)

0 2 4 8 24

Time (h)

Effects of Cortisol on Plasma IGF
  • Cortisol ↓ plasma IGF levels
  • Effect takes 24 hours

From Kajimura et al. (2003) JOE 178:91-99

effects of cortisol on plasma igfbps

2 mg/g

10 mg/g

control

IGFBP-3

ODU

IGFBP-1

ODU

0 2 4 8 24

Time (h)

Effects of Cortisol on Plasma IGFBPs
  • ↓ plasma IGFBP-3 levels
  • ↑ plasma IGFBP-1 levels
  • Cortisol induces rapid changes in plasma IGFBPs

Tilapia

From Kajimura et al. (2003) JOE 178:91-99

clinical aspects17
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
slide18

Acromegaly

-overproduction of GH

-before puberty: gigantism (excessive growth of long bones)

-in adults: causes excessive growth of cartilage

-symptoms

clinical aspects19
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
clinical aspects21
Clinical Aspects
  • Overproduction of GH
    • Acromegaly
    • gigantism
  • Underproduction of GH
    • hypopituitary dwarfism
    • Stress-induced dwarfism
  • End-organ resistance
laron s syndrome
Laron’s Syndrome
  • Defective GH receptor
  • recessive gene
  • Lethal in males
clinical aspects23
Clinical Aspects
  • Overproduction of GH
    • Acromegaly
    • gigantism
  • Underproduction of GH
    • Hypopituitary dwarfism
    • Stress-induced dwarfism
  • End-organ resistance
    • Laron’s Syndrome