Lecture for medical students

1. Lecture: 11
FUNCTIONS & CONTROL OF ANTERIOR
PITUITARY,GROWTH HORMONE.
Dr Shamshad
Majmaah University
KSA

2. Hormone secreting cells of the Ant.Pitutary gland
Cell type Hormone secreted % of total Secretory cells
Somatotrope Growth Hormone 50
Lactotrope Prolactin 10-30
Corticotrope ACTH 10
Thyrotrope TSH 5
Gonadotrope FSH,LH 20

3. Objectives
1. List the hormones secreted by the Anterior Pituitary Gland.
2. Discuss physiological actions of Growth Hormone(GH).
3. Outline the role of Somatomedins as mediators of Growth
Hormone actions.
4. Describe the mechanisms that regulate GH production & release.
5. Describe the sources,actions of somatostatin & relate it to growth
hormone control.
6. Correlate this knowledge to Clinical conditions related to hypo &
hyper of Growth Hormone.

5. Human Growth Hormone / hGH / Somatotropic Hormone
/Somatotropin
★ Human’s GH & monkey’s GH have similar biological activities
in humans and monkeys.
★ Shows species specificity.
Exerts its effects directly on almost all tissues of the body
:Proportionate growth of body

6. Synthesis of GH
➔ Single chained 191 AA
➔ Causes growth of all tissues(capable of
growing ) of the body
By:
➔ Promoting increased sizes of the cells
➔ Increased mitosis
➔ Specific differentiation of cells
Ex: bone growth cells & early muscle cells.

7. Genes for human GH
★ GH 1 (somatotropin) & GH 2 : Localized in the q22-24 region
of chromosome 17.
★ Closely related to human chorionic somatomammotropin /
placental lactogen) genes.
★ GH, human chorionic somatomammotropin, & prolactin
belong to a group of homologous hormones with growth-
promoting & lactogenic activity.

9. ★ 2-4 ng/ml (0.2 – 1mg/day)
★ Released in pulses:10 – 20
pulses / day.
★ Level varies with age
★ Transported by GH binding
proteins (GHBPs)
★ Plasma half life : 20 min.
★ Metabolised in liver and
kidney.
Plasma level & circulation

13. GH Receptors
The GH has 2 binding sites ,each site binds single -chained
membrane bound protein receptors in the target cells.
Followed by dimerization of the receptors & activation of a
tyrosine kinase enzyme known as Janus Kinase 2(Jak 2) attached
to intracellular domain
Two Jak-2 kinases phosphorylate each other & Tyrosine residues of
the receptor.
This leads to a cascade of phosphorylation reactions that results in
activation of STAT,MAP and PI3 kinase sequesnce.
This over all reactions leads to linear growth & other actions of GH

14. JAK2:Janus kinase 2
STAT:Signal Transducer & Activation of Transcription
FAK:Focal Adhesion Kinase
MAP kinase:Mitogen -Activated Protein kinase
IRS: Insulin Receptor Substrate
PI3K:Phosphotidly Inositol 3 kinase
GHR:GH receptors

16. Somatomedin(SM)/ Insulin-like growth factors /IGFs
Structural homologues of insulin with insulin-like biological activity
Defn:GH dependent hormonal peptides mediating GH action
➔ Synthesised in hepatic and extrahepatic tissues.
➔ Have autocrine ,paracrine and endocrine action
➔ Promote cell growth and division in response to stimulation of
GH
➔ Stimulate production of somatostatin
1:Somatomedins A: Insulin like Growth factors II
2:Somatomedins B :from Vitronectin
3:Somatomedin C: Insulin like Growth factor I

17. Insulin IGF-I IGF-II
Other Name Somatomedin C Somatomedin A
No.of AA 51 70 67
Source Pancreatic ß
cells
Hepatic & Extra hepatic
tissues
Diverse tissues
Level regulated by Glucose GH after birth
,nutritional status
Unknown
Plasma Levels ng/ml 0.3-2.0 10-700 peaks at puberty 300-800
Plasma binding
proteins
No Yes Yes
Physiological role Glucose
metabolism
Skeletal & cartilage
growth
Growth during fetal
development

18. Difference b/w IGF -I and IGF -II
IGF-I / Somatomedin C
● Highest production:pubertal growth
spurt.
● Receptors: similar to Insulin receptor
● Action:Stimulates systemic body
growth, and has growth-promoting
effects on almost every cell in the
body:Skeletal muscle, cartilage, bone,
liver, kidney, nerve, skin,
hematopoietic, and lung cells.
● Also regulate cellular DNA synthesis
IGF- II / Somatomedin A
● Production:fetal life
● Receptors:IGF-2 alone binds a
receptor called the "IGF-2
receptor" / mannose-6
phosphate receptor).
● Action:Believed to be a major
fetal growth factor
● The major role growth
promoting hormone during
gestation

19. General Action of GH

21. Metabolism of carbohydrates:
Decrease in the peripheral utilization of glucose for the production
of energy
Increases the deposition of glycogen in the cells
Decreases the uptake of glucose by the cells
Diabetogenic effect

22. Metabolism of protein
Accelerates the synthesis of proteins by (Anabolic effect)
★ Increasing AA transport through the cell membrane
★ Increasing transcription of DNA & RNA
★ Increasing RNA translation
★ Decreasing the catabolism of protein
★ Promoting anabolism of protein indirectly by Positive nitrogen
and phosphorus balance
★ Promote Lean Body Mass.

23. Metabolism of Fat
Mobilizes fats from adipose tissue: (Ketogenic effect)
Increases the conc. of FFA which are used for the energy
production by the cells.
During the FFA utilization for energy aceto acetic acid is produced
which is released in the body fluid and hence leads to ketosis.

24. Effects on bone and cartilage
In Embryonic stage: GH is responsible for the differentiation and
development of bone cells
Later stages:Increase growth of skeleton, length & thickness of
bones.
Increased absorption of Calcium from GIT
Increases the Increased synthesis of soluble collagen
Linear growth.

26. Table show the stimuli that
affect the GH secretions

27. Correlate the knowledge to Clinical conditions
I:Hypersecretion of GH:
1:Before puberty:Closure of epiphysis: Gigantism
➢ Increase linear growth
2:After puberty: after closure of epiphysis or growth
plate:Acromegaly
➢ Increase thickness of the bones Mainly jaw, hand and toes
II:Hyposecretion: Dwarfism :Pituitary or constitutional type
➢ Proportionate decrease in size of the body.

28. GIGANTISM

29. ACROMEGALY

30. Normal and abnormal growth : hypothyroid retain infantile proportions while
constitutional type show proportionate characteristic of their chronologic age
and sex

31. Laron Dwarfism: Rare Congenital abnormalities of
GH receptors hence Plasma conc. of GH binding
decrease and IGF-I not secreted in sufficient amount.
Show low rate of cancer and diabetes
African pygmies :
Their plasma IGF-I conc. fail
to increase in puberty.