Growth Hormones

1
Growth Hormones

• JP Slovak

2
Introduction

• Cell Cycle
• Growth
• Hypertrophy
• hyperplasia

3
GH and IGFs

• GH
• Low GH short stature
• High GH Gigantism
• Causes growth of epiphyseal plates
• Can monitor S uptake of cartilage to measure
  growth
• Hypophysectomized animals no S uptake
• Add GH S uptake

4
GH and IGFs

• Somatomedins
• GH, when injected localizes at liver
• Somatomedins are
• Found in plasma under GH control
• Have insulin like properties
• Promote S incorporation into cartilage
• IGF 1 and 2
• Similar to insulin
• At high concentration, bind to each others
  receptors
• Secreted by liver
• Not stored in liver
• IGF 2 3x more abundant
• 1 and 2 have different receptors

5
GH and IGFs

• Effect on cartilage growth
• Somatomedin hypothesis
• GH does not have a direct effect
• IGF 1 produced in proliferating chrondrocytes
• In response to GH
• GH and IGF1 have different target cells
• GH stimulates germinal cells
• IGF1 acts on resulting chrondrocytes
• Dual effector hypothesis
• GH stimultes undifferentiated cells and IGF1 acts
  in GH-primed cells

6
GH and IGFs

• Control of GH
• GHRH and SST
• IGF1 stimulates SST release
• GH acts on liver to produce IGF1
• Other hormones may use same mechanism
• GH can have diabetogenic effect

7
GH and IGFs

• Effects on stature
• Dwarfism in German Sheperds
• Recessive trait
• Causes GH deficiency
• Little mouse strain
• Decreased GH production
• Pituitaries insensitive to GHRH
• African pygmy
• Low levels of IGF1
• IGF2 in normal range

8
GH and IGFs

• Laron syndrome
• Autosomal recessive trait
• Consanguineous families
• GH normal
• Have elevated levels of GH
• Reduced IGF1 levels
• Defect in GH receptor

9
Other Hormones

• Insulin
• Dominant role in CHO homeostasis
• Diabetic children fail to grow
• Protein catabolism promoted in absence
• Increases aa incorporation in skeletal muscle
• At high levels promotes general growth
• Prolactin
• Milk synthesis
• Has various growth related functions
• Important for breast enlargement
• In rats, promotes IGF production
• Can stimulateT cell immune responses
• Important for modulation of ovary and teste
  growth

10
Other Hormones

• Placental lactogen
• Secreted by placenta
• Similar to GH
• Lacks growth promoting activity
• Found in plasma as early as 6th week
• PL increases S uptake(rats)
• Stimulates growth and induction of milk(mice)
• Mimics GH, but less potent
• Mammary development during pregnancy
• May insure adequte glucose, aa and minerals for
  fetus
• Gestational diabetes
• Counters insulin

11
Other Hormones

• Neurotropic Growth Factors
• NGF
• Production is androgen dependent
• Under control of test and thyroxine
• 10x higher in males than females
• Submandibular glands secrete NGF
• Fighting in male mice may have a role
• NGF increases size of adrenal glands
• Important for maintenece of sympathetic nervous
  system
• Similar to pro insulin
• Anabolic
• Insulin and proinsulin can compete for NGF
  receptors
• NGF internalized by retrograde axonal transport
• NGF has pleotropic effects
• Enzymes, nerve fiber growth, increase
  neurofilaments
• Directs growing sympathetic neurons
• Prevents degeneration of neurons in forebrain

12
Other Hormones

• EPO
• Red cells constant
• High altitude increases EPO
• EPO elevated by hypoxia
• Decreases by hyperoxia
• Increased metabolic rate increases EPO
• Intrarenal O2 sensor determines EPO production
• Produced mainly by the kidneys
• Liver may be source of fetal EPO
• Takes 2-3 days of stimulation to manifest itself
• Linked to anemia
• Polycythemia
• Discuss cyclist use

13
Other Hormones

• Thymic Hormones
• Thymus lies in front of heart
• In adult, removal is not detrimental
• Important in immune function
• Removal in young mice causes wasting disease
• Responsible for maturation of T cells
• Thymosin

14
Other Hormones

• PDGF
• Maintains viability of RBC
• Released during platelet aggregation
• Contraction of smooth muscle
• Role in atherosclerosis?
• Consists of a family of molecules
• Heterodimer AA, BB, AB
• 2 receptors
• One binds all three
• One binds just BB
• Evidence that they have different functions

15
Other Hormones

• Epidermal Growth Factor
• Accelerates tooth eruption in mice
• Found in salivary gland with binding protein
• Release maybe under nervous control
• Stimulates incorporation of small molecules into
  cells
• Enhances proliferation of epidermis
• Enhances growth of fetal pulmonary epithelium
• Acceleration of wound healing
• Salivary EGF in wound healing
• Is present in breast milk
• May help in development of fetal intestines
• Urogastrone similar to EGF
• Elevated during pregnancy

16
Other Hormones

• Angiogenic factors
• Tumors must have blood supply
• Angiogenic factor is derived from tumors
• Some act on endotehlium directly
• Some act indirectly to produce EDGFs
• Fibroblast Growth Factors
• Family of polypeptides
• Role in development
• Maintain neurons