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 in adults are mediated by Insulin like Growth Factor-1(IGF-1)
IGF-1 is a protein, synthesized in the liver and stimulated by GH
– – Ncbi.nlm.nih.gov.

4. Target organs- tissues with GHR/RTK
Target organs are the ones with GH hormone /Tyrosine Kinase receptors. (TRK)
Major target organs/tissues are :
Bones (Chondrocytes); Liver, Adipose tissues, Skeletal muscles
and Kidneys

5. Target organs - GHR/RTK Demerization
GHR are predominantly present as dimmer with 3 domains :
Extracellular, membranous and Cytoplasmic
These receptors are mobile and single chain
The 2 receptors are held together by trans membrane helices.
The process is called dimerization

6. GH – the receptors (GHR/RTK)/Enzyme 3 Domains

7. Factors that increase GH synthesis/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

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

9. Factors affecting GH synthesis

10. GH – Regulation of secretion/synthesis Major Regulators - 2
Secretion of GH 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)

11. Regulation of GH synthesis
There are 2 pathways for the regulation of GH synthesis
Neuro endocrine /long loop/Indirect regulation
Pituitary - somatic/direct/short loop regulation

12. Regulation of GH

13. Neuro endocrine regulation
It is the interaction B/W the circulating level of GH/IGF-1 and hypothalamic – Pituitary axis
Low GH/IGF-1 level stimulates the hypothalamus to release GnRH which activates ant.pitu.to ↑ GH/IGF-1 synthesis
Opposite is true when GH/IGF-1 is high by ↑ the GHIH
(Growth hormone Inhibiting hormone}

14. Pituitary- Somatic pathway Pituitary – GH axis
It is the interaction B/W the circulating level of GH/IGF -!
Low GH/IGF -1 stimulates Ant. pituitary to ↑ the synthesis of GH to ↑ the serum level of GH/IGF- 1
Opposite is true when circulating level is of GH/IGF -1 is high

15. 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)

16. GH - Mechanism of action - Genomic Summary
GH binds with the receptor RTK – causes Demerization and auto phorylation of the tyrosine residues of RTK – 1st step
Phosphorylation of the JAK2 and the intracellular tyrosine residues near RTK takes place in the next /2nd step
STAT proteins are generated by the RER of the target organs; get attracted, phosphorylated and forms dimmer
STAT are transcription factors and are translocated to the DNA.
Transcription of mRNA; move to cytoplasm and translates proteins and enzymes to execute the actions of GH

17. GH – Genomic mechanism of action

18. 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 and
Activation of both the receptor and receptor associated enzyme- Janus Kinase2 (JAK2)
There is Rotation of the Cytoplasmic domain of GHR to remove the inhibitory Pseudokinase domain of one of the JAK2

19. 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 (HRE)for the transcription of mRNA which moves to the cytoplasm
mRNA Translates a no of Proteins and enzyme to execute GH actions
STATS are synthesized in RER of target cell and act as transcription factors for the STAT genes

20. GH – Genomic action

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

22. GH- non genomic mechanism

23. 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 (IP3) , Diacyl glycerol (DAG)and Nitric Oxide(NO) –
All of them act as 2nd messenger which execute the GH action

24. GH- Non genomic mechanism of action Quick/rapid action

25. GH – the Metabolic role in general
GH is an anabolic hormone that promotes the body growth through its actions on the :
Protein metabolism
Lipid and Carbohydrate metabolism
Growth of long bones and availability of Ca and Po4

26. GH – Metabolic actions

27. 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

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

29. 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

30. GH and bones – ↑ 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 especially the long ones

31. 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

32. GH – the excess in children and adults
Excess of GH in children results in :
Gigantism or Giantism when epiphysis is not united and increases the length of long bones of limbs
Acromegaly in Adults with closed epiphysis that increases the mass but not the length of long bones

33. GH – the Deficiency In Children/adults results in dwarfism
Deficiency of GH in children results in short stature and is called Dwarfism or pituitary dwarfism
All physical parts of the body are in appropriate proportion but the rate of growth is greatly reduced
GH deficiency in adults is rare