Growth Harmone; secretion, functions and metabolism

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.

Growth Harmone


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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