1. Growth hormone

2. Objectives The student should be able to:
Identify the hormones that affect growth.
Describe the metabolic effects of GH.
Identify relationship between GH and insulin-like growth factors.
Explain the functions of GH.
Define the factors that influence GH secretion.
Describe GH abnormalities.

3. Hormones regulating growth
1) Growth hormone.
2) Thyroid hormones:
Growth is severely stunted in hypothyroid children.
Hypersecretion does not cause excessive growth.
3) Insulin & IGF 1:
Deficiency often blocks growth.
Hyperinsulinism often spurts excessive growth.
4) Androgens:
Play a role in pubertal growth spurt, stimulate protein synthesis in many organs.
Effects depend on presence of GH.

4. Growth hormone (GH) (= Somatotropin)
Somatotropin: tropic hormone that affects somatic cells.
Growth hormone is a 191- amino acid, single-chain synthesized, stored, and secreted by somatotropic cells within anterior pituitary gland.
It is metabolized rapidly in liver.
Short duration of action (20 minutes).

5. GH Functions Stimulates growth:
Hypertrophy: increase in size of cells.
Example: increase in bone thickness.
Stimulates cell reproduction:
Increased rate of mitosis.
Hyperplasia: increase in number of cells & proliferation rate.
Example: increase in bone length.

6. Metabolic functions of GH
1) Protein synthesis (Anabolic):
Adequate insulin & carbohydrates necessary for GH to be effective.
 Amino acid Transport inside cells  protein accumulation in all cells.
 DNA Transcription to form mRNA  protein synthesis.
 RNA Translation  protein synthesis.
2) Lipolytic & Ketogenic effect:
 Mobilization & use of fatty acids for supplying energy.
So, excess hormone  ketosis.

7. 3)  Utilization of carbohydrate for energy production:
 Uptake of glucose by cells  blood glucose (diabetogenic effect).
 Use of glucose for energy production due to  utilization of fatty acids for energy.
It inhibits hexokinase enzyme  inhibits glucose uptake by muscles (opposite to insulin effect).
 Hepatic glucose output (stimulates glycogenolysis).
 Insulin output  burn out of beta cells of pancreas (pituitary diabetes).

8. GH Function (Indirect Effect)
Most growth occurs through the indirect method.
GH acts as a tropic hormone acting on the liver to produce Insulin-like Growth Factor-1 (IGF-1).
Insulin-like growth factor I (somatomedin C)   growth promoting activities in many tissues and cartilage with a prolonged duration of action (20 hours).

11. Chondrogenesis & bone growth
In young: (before union of epiphysis) GH stimulates chondrogenesis (proliferation of epiphyseal cartilage & widening of epiphyseal plates). Stimulation of osteoblasts   bone matrix   length of long bones.
In adult: (after union of epiphysis) linear growth is impossible.

12. Growth Hormone Regulation
hypothalamus
growth hormone releasing hormone (GHRH)
growth hormone inhibiting hormone Somatostatin (GHIH)
anterior pituitary
growth hormone (GH)
liver
Insulin-like growth factor 1 (IGF-1)
GH half - life
= min.

13. Negative Feedback
High levels of IGF-1 Stimulates somatostatin GHIH (=SS)  decreased secretion of GH.
High levels of GH inhibits GHRH.

14. GH Secretion Secreted in bursts (not continuous).
GH is released most during sleep:
optimal at night time.
Changing sleeping pattern affects GH release.
GH production declines with age.

15. Factors affecting GH secretion
Factors stimulate GH
Factors inhibit GH
1- Hypoglycaemia
2- Protein rich diet
3-  Amino acid in blood (as Arginine)
4- Exercise
5- Stress
6- Sleep (8 hours)
7- Glucagon
8- Ghrelin
1- Hyperglycemia
2- Free fatty acids
3- Excess GH feeds back to inhibit its own secretion
4- Excess Cortisol

16. HYPOPITUITARISM 1- DWARFISM
 Growth hormone during childhood.
Characterized by:
Proportionate dwarfism (short stature): Features of body are proportionate to each other, but rate of development is decreased. Patient at age of 20 may has body development of a child at 10 years.
No thyroid deficiency.
No adrenocortical deficiency.
No mental retardation (Wise person with small stature).
Treatment: Synthetic Growth hormone

17. DWARFISM
In one type of dwarfism (the African pygmy and the Lévi-Lorain dwarf), the rate of growth hormone secretion is normal or high, but there is a hereditary inability to form somatomedin C, which is a key step for the promotion of growth by growth hormone.

18. 2- Simmond’s disease (=Pituitary Cachexia)
Cause:
a) Damage of pituitary by Ischemia & Tumor.
b) Postpartum hemorrhage  pituitary necrosis (Sheehan's Syndrome).
C/P: Panhypopituitarism ( GH, TSH, ACTH, FSH & LH).
Premature senility (= Progeria), loss of hair and body weight & shrunken skin.
Asthenia (muscular weaknes) & ↓ Mental Activity.
Thyroid deficiency  low BMR &  serum cholesterol.
Adrenocortical deficiency  hypoglycemia.
Gonadal deficiency (hypogonadism).

19. HYPERPITUITARISM 1- Gigantism (Vertical Growth)
 GH by Acidophils in anterior pituitary before union of epiphysis (in children).
Cause:
Pituitary Adenoma
Tumour formed by pituitary gland.
Secretes excessive GH / IGF-1
Non cancerous.

20. Gigantism Clinical picture:
All body tissues grow rapidly i.e. general overgrowth of skeleton  person becomes a Giant.
High BMR (direct effect of GH on metabolic activity + effect of TSH).
Hyperglycemia & diabetes mellitus  lowered general resistance.
Low gonadotropins  Hypogonadism.
Short life, if survives till adulthood  Acromegaly.

22. World’s Tallest Man Robert Wadlow (1918-1940)
8 feet 11 inches and 439 pounds when he died

23. Acromegaly (Lateral Growth)
Acro = extremity as hands and feet.
Megaly = large.
↑↑ GH by Acidophil After union of epiphysis (in Adult).
Closed epiphyseal plate → Bone lengthening stopped.
Bone width increases.
Slow progression

24. Physical Effects of Acromegaly
Bone thickening
Protruding lower jaw (= prognathism) & upper jaw, supraorbital ridge & separation of teeth coarsening of facial features (bone deformities).
Hands and feet (=acral parts) are enlarged(thick, broad fingers).
Bowing of spine (kyphosis).

25. Physical Effects of Acromegaly
Soft tissue enlargement:
- Deeper voice because larynx enlarges
- Bigger tongue and lips that affects breathing
- Cartilages in nose and ears enlarge making nose and ears broader.
Impaired muscle movements:
Enlargement of bones crushes
peroneal nerve in knee.
Nerve cannot send messages to
leg to trigger walking motion.

26. Acromegaly: Heart Defect
Cardiac effects:
Heart grows bigger in order to pump out sufficient blood.