1. Growth Hormone – A Pituitary Hormone Lecture NO : 2nd MBBS
Dr Muhammad Ramzan

2. Growth Hormone (GH ) – the definition Somatotropin
A polypeptide hormone (191 AA) secreted by the anterior pituitary gland that promotes the body growth
It is also called as Somatotropin
GH influences the metabolism of proteins, lipids and carbohydrates

3. GH – the background
Primary function of the GH is the promotion of linear growth especially of the long bones
GH is present in intra uterine life as IGF-2 for faetal growth and continues as such independently
Most of the growth promoting effects are mediated by Insulin like Growth Factor-1(IGF-1)
IGF-1 is a protein, synthesized in the liver and stimulated by GH

4. Target organs- tissues with GHR/RTK
Target organs are the ones with GH Receptors : GHR or
Tyrosine Kinase/ RTK (A single chain)
The densely populated tissues are ; Liver, Adipose tissues, Skeletal muscles, bones (Chondrocytes) and Kidneys
GHR are predominantly present as dimer with 3 domains – Extracellular ,transmembrane and Cytoplasmic – are mobile
The 2 receptors are held together by trans membrane helices

5. GH – the receptors (GHR/RTK)/Enzyme Extra cellular,transmembrane and cytoplasmic domains

6. Factors that increase GH secretion
GH is also promoted by physical; chemical, traumatic and surgical stresses
Young age in Children and adolescence
Good nutrition
prolonged exercise and hypoglycemia
Low levels of IGF-1 in blood

7. Factors that reduce GH secretion
Old age
Malnutrition in children
Chronic diseases especially of liver that reduce IGF-1 synthesis
Hyperglycemia
Emotional stress
Glucose given orally or I/V

8. GH – Regulation of secretion Major Regulators - 2
Secretion of is stimulated by the hypothalamic GH Releasing hormone – GHRH
Is inhibited by the GH Inhibitory hormone GHIH from Hypothalamus and :
Serum level of Insulin like Growth Factor – IGF
IGF- I level is inversely proportional to GH level

9. Regulation of GH

10. GH - Mechanism of action 2 pathways
GH is a protein hormone and its mechanism of action is similar to the like ones- 2nd messenger system
It acts through 2 mechanisms:
Genomic through activation of Genes – Delayed
Non genomic via 2nd messenger Rapid (minutes)

11. GH - Mechanism of action (Genomic) Delayed action
The major players are the GH receptor, Janus Kinase 2 , Signal Transducers and Activators of Transcription (STAT)
Binding of the GH with receptor causes its dimerization:
the activation of both the receptor and non receptor enzyme- Janus Kinase2 (JAK2)
There is Rotation of the Cytoplasmic domain of GHR to remove the inhibitory Pseudokinase domain of one of the JAK2

12. GH - Mechanism of action (Genomic) cont
GH - Mechanism of action (Genomic) cont. Translocation of STAT to Nucleus
This removal restores the Kinase activity of the other JAK2 and vice versa which promotes the Phosphorylation of :
Intracellular enzymes and proteins including the STAT factors
STATS are Tranalocated to the nuclear genes for transcription of mRNA which moves to the cytoplasm (hormone response element)
Translates a no of Proteins and enzyme to execute GH actions

13. Genomic or JAK2 – STAT pathway

14. GH- Non genomic mechanism 2nd messenger cGMP.
Binding of GH with the receptor causes its activation (Tyrosine Phosphorylation) as well as that of RAS activating Protein
Activation of RAS protein results in the conversion of GDP to GTP that activates the membranous enzyme :
Adenylate Cyclase to alter GTP to cGMP as 2nd messenger 1.
cGMP alters the activity of the proteins and enzymes to execute the GH actions

15. GH - Non genomic mechanism cont. IP3.DAG and NO as 2nd messenger
Phospholipase C is another Membranous enzyme that is also activated by the cGMP
cGMP acts on the Phospho Inositol Diphosphate (PIP2 ) and convert it into Inositol Tri phosphate :
Diacylglycerol (DAG)and Nitric Oxide(NO) - All of them act as 2nd messenger which execute the GH action

16. GH- non genomic mechanism

17. Metabolic role of the GH in general
GH primarily promotes body growth through its actions on the :
Protein metabolism
Lipid and
Carbohydrate metabolism
Growth of long bones and availability of Ca and Po4

18. GH – Action on protein metabolism stimulates protein synthesis
It ↑ proteogenesis by increasing the entry of AAs in the cells
Promotes growth by ↑in the no of cells, muscle and bone mass
It stimulates genetic expression; mRNA and its translation into proteins and enzymes
GH inhibits protein degradation - Proteolysis

19. GH – effects on Lipid metabolism promotes Lipolysis
GH increases Lipolysis and enhances serum level of fatty acids
Promotes the oxidation of FAs to satisfy the growing energy needs of the growth
Reduces the Lipogenesis and reduces Adipose tissue mass `

20. Effects on CHO metabolism Hyperglycemic
GH prevents the entry of glucose in the cells and increases blood glucose level, is hyperglycemic
Its actions are antagonistic to the actions of Insulin and promotes Insulin Resistance
GH promotes Glycogenolysis and :
Reduces Glycogenesis

21. Actions of GH On bones – Increases length and mass of long bones
GH promotes retention of Ca and Po4 through increased GIT absorption and resorption by kidney
It promotes Osteogenesis and Ossification
Promotes the length and mass of bones especially the long ones

22. GH- the effects

23. GH – Secretion abnormalities
GH may be secreted in excess or there may be deficiency of its secretion/synthesis
The excess or deficiency may happen in children when epiphysis of long bones are not united or :
It may occur in adults when epiphysis are closed
Clinical manifestations are quite different in both the conditions

24. GH – the excess in children and adults
Excess of GH in children results in :
Gigantism or Giantism when epiphysis is not united and
Acromegaly in Adults with closed epiphysis

25. Excess of GH in Children - Giantism

26. Excess of GH in adults - Acromegaly
GH excess in adults with closed epiphysis produce the clinical condition called Acromegaly
They have no linear growth but there is increase in the size of the Bones of Lower jaw and carpal bones respectively
There is Increase in soft tissue mass especially of hands, feet
and viscera like liver

27. Acromegaly large size of lower jaw

28. Deficiency of GH In Children results in dwarfism
Deficiency of GH in adults is rare
Deficiency of GH in children results in :
short stature and is called Dwarfism or pituitary dwarfism

29. Deficiency of GH in children