GROWTH HORMONE
Source of Secretion
Growth hormone is secreted
by somatotropes which are the acidophilic cells of anterior pituitary.
Chemistry, Blood
Level and Daily Output
GH is protein in nature,
having a single-chain polypeptide with 191 amino acids. Its molecular weight is
21,500. Basal level of GH concentration in blood of normal adult is up to 300
g/dL and in children, it is up to 500 ng/ dL. Its daily output in adults is 0.5
to 1.0mg.
Transport
Growth hormone is transported
in blood by GH-binding proteins (GHBPs).
Half-life and
Metabolism
Half-life of circulating
growth hormone is about 20 minutes. It is degraded in liver and kidney.
Actions of Growth
Hormone
GH is responsible for the
general growth of the body. Hypersecretion of GH causes enormous growth of the body,
leading to gigantism. Deficiency of GH in children causes
stunted growth, leading to dwarfism.
GH is responsible for the
growth of almost all tissues of the body, which are capable of growing. It
increases the size and number of cells by mitotic division. GH also causes specific differentiation of certain types of cells like
bone cells and muscle cells. GH also acts on the metabolism of all the three
major types of foodstuffs in the body,
viz. proteins, lipids and carbohydrates.
1. On metabolism
GH increases the synthesis of
proteins, mobilization of lipids and conservation of carbohydrates.
a. On protein
metabolism
GH accelerates the synthesis of
proteins by:
i. Increasing amino acid transport
through cell membrane: The concentration of amino acids in the cells
increases and thus, the synthesis of proteins is accelerated.
ii. Increasing ribonucleic acid
(RNA) translation:
GH increases the translation of RNA in
the cells Because of this, ribosomes are
activated and more proteins are synthesized. GH can increase the RNA
translation even without increasing the amino acid transport into the cells.
iii. Increasing transcription of
DNA to RNA: It also stimulates the transcription of DNA to RNA. RNA, in turn
accelerates the synthesis of proteins in the cell.
iv. Decreasing catabolism of
protein: GH inhibits the breakdown of cellular protein. It helps in the
building up of tissues.
v. Promoting anabolism of proteins
indirectly: GH increases the release of insulin (from β-cells of
islets in pancreas), which has
anabolic effect on proteins.
b. On fat metabolism
GH mobilizes fats from adipose tissue.
So, the concentration of fatty acids increases in the body fluids.
These fatty acids are used for the
production of energy by the cells. Thus, the proteins are spared.
During the utilization of fatty acids
for energy production, lot of acetoacetic acid is produced by liver
and is released into
the body fluids, leading to ketosis. Sometimes, excess mobilization of fat from
the adipose tissue
causes accumulation of fat in liver, resulting in fatty liver.
c. On carbohydrate metabolism
Major action of GH on carbohydrates is
the conservation of glucose.
Effects of GH on carbohydrate
metabolism:
i. Decrease in the peripheral utilization
of
glucose for the production of energy: GH reduces the
peripheral utilization of glucose for
energy production. It is because of the formation
of acetyl-CoA during the metabolism of
fat, influenced by GH. The acetyl-CoA inhibits the
glycolytic pathway. Moreover, since
the GH increases the mobilization of fat, more fatty acid
is available for the production of
energy. By this way, GH reduces the peripheral utilization of
glucose for energy production.
ii. Increase in the deposition of
glycogen in the cells: Since glucose is not utilized for energy
production by the cells, it is
converted into glycogen and deposited in the cells.
iii. Decrease in the uptake of glucose
by the cells:
As glycogen deposition increases, the
cells become saturated with glycogen. Because of
this, no more glucose can enter the
cells from blood. So, the blood glucose level increases.
iv. Diabetogenic effect of GH:
Hypersecretion of GH increases blood glucose level enormously.
It causes continuous
stimulation of the β-cells in the islets of Langerhans in pancreas and
increase in secretion of insulin. In
addition to this, the GH also stimulates β-cells directly
and causes secretion of insulin.
Because of the excess stimulation, β-cells are burnt out at
one stage. This causes
deficiency of insulin, leading
to true
diabetes mellitus or
full-blown
diabetes mellitus. This effect of GH is
called the diabetogenic
effect.
2. On bones
In embryonic stage, GH is responsible
for the differentiation and development of bone cells. In later
stages, GH increases the growth of the
skeleton. It increases both the length as well as the thickness of
the bones. In bones, GH increases:
i. Synthesis and deposition of
proteins by
chondrocytes and osteogenic cells
ii. Multiplication of chondrocytes and osteogenic cells by enhancing the
intestinal calcium absorption
iii. Formation of new bones by
converting chondrocytes into osteogenic cells
iv. Availability of calcium for
mineralization of bone matrix.
GH increases the length of the bones,
until epiphysis fuses with shaft, which occurs at the time of puberty. After
the epiphyseal
fusion, length
of the bones cannot be increased. However, it stimulates the osteoblasts strongly. So, the
bone continues to grow in thickness throughout the life. Particularly, the
membranous bones such as the jaw bone and the skull
bones become thicker under the influence of GH.
Hypersecretion of GH
before the fusion of epiphysis with the shaft of the bones causes enormous
growth of the skeleton, leading to a condition called gigantism. Hypersecretion
of GH after the fusion of epiphysis
with the shaft of the bones
leads to a condition called acromegaly.
Mode of Action of GH
– Somatomedin
GH acts on bones, growth
and protein metabolism through somatomedin secreted by liver. GH stimulates
the liver to secrete somatomedin.
Sometimes, in spite of normal secretion of GH, growth is
arrested (dwarfism) due to the absence or deficiency of
somatomedin.
Somatomedin
Somatomedin
is defined as a substance through which growth hormone acts. It is
a polypeptide with the
molecular weight of about
7,500.
Types of
somatomedin
Somatomedins are of two
types:
i. Insulin-like growth factor-I
(IGF-I), which is also called somatomedin C
ii. Insulin-like growth
factor-II. Somatomedin C (IGF-I) acts on the bones and protein metabolism. Insulin-like
growth factor-II plays an important role in the growth of fetus.
Duration
of action of GH and somatomedin C
GH is transported in blood
by loose binding with plasma protein. So, at the site of action, it is released
from plasma protein rapidly. Its action also lasts only for a short duration of
20 minutes. But, the somatomedin C binds with plasma proteins very strongly.
Because of this, the molecules of somatomedin C are released slowly from the
plasma proteins. Thus, it can act continuously for a longer duration. The action
of somatomedin C lasts for about 20 hours.
Mode of
action of somatomedin C
Somatomedin C acts through
the second messenger called cyclic AMP.
Growth
hormone receptor
GH receptor is called growth
hormone secretagogue (GHS) receptor. It is a transmembrane receptor, belonging to
cytokine receptor family. GH binds with the receptor situated
mainly in liver cells and forms the hormonereceptor complex. Hormone-receptor complex induces various
intracellular enzyme pathways, resulting in somatomedin secretion. Somatomedin in turn, executes the
actions of growth hormone.
Regulation of GH
Secretion
Growth hormone secretion
is altered by various factors. However, hypothalamus and feedback mechanism
play an important role in the regulation of GH secretion
GH secretion is stimulated
by:
1. Hypoglycemia
2. Fasting
3. Starvation
4.
Exercise
5. Stress and trauma
6. Initial stages of
sleep.
GH secretion is inhibited
by:
1. Hyperglycemia
2. Increase in free fatty
acids in blood
3. Later stages of sleep.
Role of
hypothalamus in the secretion of GH Hypothalamus regulates GH
secretion via three
hormones:
1. Growth
hormone-releasing hormone (GHRH):
It increases the GH
secretion by stimulating the somatotropes of anterior pituitary
2. Growth hormone-releasing
polypeptide (GHRP): It increases the release of GHRH from hypothalamus
and GH from pituitary
3. Growth hormone-inhibitory
hormone (GHIH) or somatostatin: It decreases the GH secretion.
Somatostatin is also secreted
by delta cells of islets of Langerhans in pancreas.
These three hormones are
transported from hypothalamus to anterior pituitary by
hypothalamohypophyseal portal blood
vessels.
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