Learning Objectives
- By the end of lecture, students should
be able to - Mention the source of growth
hormone - State the release and regulation of
growth hormone - Summarize the metabolic and
growth effects of growth hormone - Explain the role of somatomedin C
- Explain the abnormalities related to
growth hormone
DWARFISM
- A mother and father bring there child of 7
years old to their new pediatrician
concerned with their son’s growth. The
parents say he is shorter than both the
males and females in his class and seems
to have lower muscle strength and mass in
comparison with his peers. The doctor
takes measurements and finds that their
son is approximately 22% shorter than the
average male height at his age. The doctor
also notes that despite the shorter height,
the body and limb proportions are
relatively normal, though there is an
increased distribution of fat throughout
the body
Growth Hormone
- Growth hormone, also called somatotropic
hormone or somatotropin - Small protein molecule contains 191 amino
acids in a single chain - Molecular weight of 22,000.
- Causes growth of almost all tissues of the
body - Promotes
- Increase in size of the cells and increased
mitosis - Development of greater numbers of cells
- Specific differentiation of cells such as
bone cells and muscle cells.
- Growth hormone receptor—620
amino acid protein - Transmembranous protein
- Acts via enzyme activation—
intracellular signaling pathway - Plasma concentration– 0-3ng/mL
- Increased rate of protein synthesis in most
cells of the body - Increased mobilization of fatty acids from
adipose tissue - Increased free fatty acids in the blood, and
increased use of fatty acids for energy; - Decreased rate of glucose utilization
throughout the body.
Growth hormone enhances body protein, uses
up fat stores, and conserves carbohydrates
Protein Metabolism (Anabolic)
Growth Hormone
- Enhances transport of amino acids into the interior of
the cells - Increases the amino acid concentrations in the cells
results in increased protein synthesis - Stimulates the transcription of DNA in the nucleus leads
to formation of increased quantities of RNA - Increases RNA translation, causing protein to be
synthesized in greater amounts by the ribosomes in the
cytoplasm - Restricts catabolism thus decreases the breakdown of
cell protein - Mobilizes free fatty acids from adipose tissue to supply
energy to the body cells, thus a potent “protein sparer.”
Fat Metabolism (Ketogenic)
Growth Hormone
- Causes release of fatty acids from adipose
tissue thus increasing the concentration of
fatty acids in the body fluids - Enhances conversion of fatty acids to acetyl-
CoA and its utilization for energy - Increase lean body mass
- Large quantities of acetoacetic acid (ketone
body) formed by liver and released into the
body fluids, causing ketosis - A KETOGENIC HORMONE
- Can cause fatty liver
Carbohydrate Metabolism (Diabetogenic)
Growth Hormone
- Decreases glucose uptake in tissues such
as skeletal muscle and fat - Increases glucose production by the liver
- Increased insulin secretion.
- Growth hormone–induced “insulin
resistance” - Growth hormone decreases insulin’s actions
- uptake and utilization of glucose in skeletal
muscle and adipose tissue - To inhibit gluconeogenesis by the liver
- Leads to increased blood glucose
concentration and compensatory increase in
insulin secretion - Mechanism for increased blood glucose is
unknown - Probably increase free fatty acids reduce
sensitivity of the cells to insulin effects - Adequate insulin activity and adequate
availability of carbohydrates are required for
growth - Insulin promotes transport of amino acid
into the cells
Cartilage and Bone Growth
Growth Hormone
- Increases deposition of protein by the
chondrocytic and osteogenic cells that
cause bone growth, - Increased rate of reproduction of these
cells - Conversion of chondrocytes into
osteogenic cells, thus causing deposition
of new bone.
- Long bones grow in length at the epiphyseal
cartilages
- Growth hormone causes deposition of new
cartilage initially and followed by its
conversion into new bone - Results in lengthening of the shaft and
pushing the epiphyses farther - GH stimulates osteoblasts thus makes bones
thicker throughout life - Thickening of bones- membranous bones.
- Jaw bones – forward protrusion of the chin and
lower teeth. - The skull – bony protrusions over the eyes
Somatomedins – IGF
- GH causes the liver and other tissues to form
several small proteins called somatomedins - Also known as insulin like growth factors
- Potent effect of increasing bone growth– IGFs
- 4 somatomedins – somatomedin C (IGF-I),
molecular weight 7500 - Pygmies of Africa have congenital inability to
synthesize somatomedin C - Plasma concentration of GH is either normal or
high but diminished amounts of somatomedin C
in plasma- have small stature - Known as Lévi-Lorain dwarf
ACTIONS
GH half life less than 20 minutes – somatomedin C half life 20 hours
Regulation of GH Secretion
Regulation of GH
Regulation of Growth Hormone
Role of the Hypothalamus
- Release of growth hormone is controlled by growth hormone releasing hormone(GHRH) and growth hormone inhibitory hormone(GHIH)
- Hypothalamic nucleus that causes secretion of GHRH is the ventromedial nucleus
- Similar area that is sensitive to blood glucose concentration, causing satiety in hyperglycemic states and hunger in hypoglycemic states
- GHRH predominates over GHIH
Growth Hormone – Abnormalities
GIGANTISM– over secretion of growth hormone before puberty
ACROMEGALY– over secretion of growth hormone after puberty
- Alam Channa– shrine of sufi saint—height was 7 feet 6
inches - Giant Gonzalez- Jorge González– a Basketball player
&Wrestler– massive height of 7 feet 6 inches - The Great Khali -Dalip Singh Rana, an Indian
professional wrestler, actor and powerlifter– height is
7 Feet 1 inch - The Big Show- Paul Donald Wight is an American
professional wrestler– height – 7 feet - Maurice Tillet- French Wrestler after whom the Ogre
character Shrek is said to be created, suffered from
acromegaly. Since his problem started late, he could
not gain extra height like other. He measured 1.7
meters
Growth Hormone
- DWARFISM under secretion of growth
hormone - The Little Couple– American reality
television series features Bill Klein and
Jennifer Arnold, who both have
skeletal dysplasias. Arnold is 96.5 cm
(3’2″) and Klein 122 cm (4 feet) tall - Jen is a pediatrician and completed
masters of medical education
Panhypopituitarism in Adults
- Panhypopituitarism – decreased secretion of
all the anterior pituitary hormones –
congenital or pituitary tumor
Causes: - Craniopharyngiomas or chromophobe
tumors compress the pituitary gland - Thrombosis of the pituitary blood vessels
- when a new mother develops
circulatory shock after the birth of her
baby – sheehan’s syndrome
Panhypopituitarism in Adults
Effects
- Hypothyroidism
- Lethargic person
- Depressed production of glucocorticoids
- Sexual functions are lost due to
suppressed secretion gonadotropic
hormones - Weight gain – lack of fat mobilization by
growth, adrenocorticotropic and thyroid
hormones
Treatment
- Administration of adrenocortical and thyroid
hormones
Applied– Under secretion
- Dwarfism
- Generalized deficiency of anterior pituitary
hormones in childhood - Rate of development decreased, growth
affected in a proportionate manner - Not pass through puberty and never secretes
sufficient quantities of gonadotropic
hormones to develop adult sexual functions. - Only GH is deficient – mature sexually and
occasionally reproduce - African pygmy and the Lévi-Lorain dwarf (IGF
deficiency) - Treatment
- Human GH – synthesized by E. coli bacteria
as a result of recombinant DNA technology
Applied– Over secretion
- Gigantism
- Before puberty– over secretion of growth
hormone - Acidophilic tumors
- All body tissues grow rapidly
Effects - 8 feet giant
- Hyperglycemia – DM
- Death can occur in early adulthood
- Treatment
- Microsurgical removal of the tumor
- By irradiation of the pituitary gland
Acromegaly
- Acidophilic tumor– after puberty
- Effects
- Cannot grow taller epiphysis has fused
- Bones become thicker
- Soft tissues continue to grow.
- Bones of the hands and feet – membranous
bones, like cranium, nose, forehead, supraorbital
ridges, lower jaw bone, vertebrae - Lower jaw and forehead protrudes forward
- Nose increases twice normal size
- Feet require size 14 or larger shoes
- Fingers thickened and hands are twice normal
size - Vertebrae bent back, kyphosis
- Large tongue – liver, kidneys, enlarged
Maurice Tillet–Oregon shrek
GH & Aging
- 50-year-old person without GH for
years looks like person aged 65 - Reason
- Decreased protein deposition in
most tissues of the body - Increased fat deposition
- Increased wrinkling of the skin
- Diminished rates of function of
some of the organs - Diminished muscle mass and
strength