Transcript growth hormone

Growth hormone
Objectives
The student should be able to:
Identify the hormones that affect growth.
Describe the metabolic effects of GH.
Identify relationship between GH and insulinlike growth factors.
Explain the functions of GH.
Define the factors that influence GH secretion.
Describe GH abnormalities.
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.
Growth hormone (GH)
(= Somatotropin)
• Somatotropin: tropic hormone that affects
somatic cells.
• Growth hormone is a 191- amino acid, singlechain synthesized, stored, and secreted by
somatotropic cells within anterior pituitary
gland.
• It is metabolized rapidly in liver.
• Short duration of action (20 minutes).
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.
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.
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).
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).
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.
Growth Hormone Regulation
hypothalamus
growth hormone
releasing
hormone (GHRH)
growth hormone
inhibiting hormone
Somatostatin (GHIH)
anterior pituitary
growth hormone
(GH)
GH half - life
= 20 - 30 min.
liver
Insulin-like growth
factor 1 (IGF-1)
Negative Feedback
• High levels of IGF-1
Stimulates somatostatin
GHIH (=SS)  decreased
secretion of GH.
• High levels of
inhibits GHRH.
GH
GH Secretion
• Secreted in bursts (not
continuous).
• GH is released
during sleep:
most
– optimal at night time.
– Changing
sleeping
pattern affects GH
release.
• GH production declines
with age.
Factors affecting GH secretion
Factors stimulate 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
Factors inhibit GH
1- Hyperglycemia
2- Free fatty acids
3- Excess GH feeds back to
inhibit its own secretion
4- Excess Cortisol
HYPOPITUITARISM
1- DWARFISM
•  Growth hormone during childhood.
• Characterized by:
1. 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.
2. No thyroid deficiency.
3. No adrenocortical deficiency.
4. No mental retardation (Wise person with small
stature).
• Treatment: Synthetic Growth hormone
DWARFISM
• In one type of dwarfism (the
African pygmy and the LéviLorain 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.
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).
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.
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.
World’s Tallest Man
Robert Wadlow (1918-1940)
8 feet 11 inches and 439 pounds when he died
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
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).
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.
Acromegaly: Heart Defect
Cardiac effects:
• Heart grows bigger in order to pump out sufficient blood.