In this article we will discuss about:- 1. Meaning of Growth Hormones 2. Mechanism of Action of Growth Hormones 3. Regulation of Secretion 5. Applied Aspects.
Meaning of Growth Hormones:
Growth hormone (GH) also known as somatotropic hormone and is a peptide hormone secreted by acidophils of the anterior pituitary gland. GH is stored in large, dense granules present in acidophil cells.
It is a single chain polypeptide with molecular weight of 22,000 having 191 amino acids and two disulphide bridges. As the name indicates, its action is on the growth of the body. It stimulates somatic growth and development and helps to maintain lean body mass and bone mass in adults.
Mechanism of Action of Growth Hormones:
i. Receptors for growth hormone are present on the plasma membrane of cells.
ii. Belong to cytokine family of receptors.
iii. Presence of excess of GH down regulates the synthesis of its receptors.
iv. Many hours must elapse after administration of GH before anabolic and growth-promoting actions of the hormones to become evident.
v. Most of the actions of GH require the production of GH induced somatomedin C or insulin-like growth factor (IGF).
vi. The plasma half-life of IGF is much longer than that of GH.
Actions of the hormone can be broadly classified into two types:
a. Indirect growth promoting action
b. Direct anti-insulin action.
1. Indirect growth promoting action (Figs 6.9 and 6.10) is due to the action of growth hormone on liver. When the hormone acts on liver, liver secretes somatomedin C or insulin-like growth factor (IGF- I). This substance acts on skeletal and extraskeletal compartments.
i. Skeletal compartment:
When somatomedin acts on epiphyseal plate present between the long bones, the epiphyseal plate gets widened. This gives space for the chondrogenesis of the long bones. The long bones grow linearly. Hence, the height of the person increases. The long bones can grow only up to the age of about 18-20 years beyond which the epiphyseal plates get fused with long bones and there can be no more linear growth of body.
ii. Extra-skeletal compartment:
This in general refers to the growth of organ and tissues. The growth is brought about by hyperplasia (stimulating mitotic cell division and hence increase in cell number) and hypertrophy (increase cell size). The various tissues in the body grow. There will be increased protein synthesis because of which it brings about positive nitrogen balance. The proteins synthesized are incorporated for the growth of the organs.
The various parts of the body do not grow in equal proportion at the same time. The growth of the different parts of the body based on chronological age has been shown in Fig. 6.11.
2. Direct anti-insulin action:
This can be brought about in the target organs in presence of Cortisol (permissive action of Cortisol is required.
i. On carbohydrate metabolism:
It is a hyperglycemic agent. Increases the blood glucose level by:
a. Decreasing the peripheral utilization of glucose.
b. Increased gluconeogensis in liver.
Uncontrolled secretion of GH for a long time brings about increase in blood glucose level. This leads to increase stimulation of beta cells of islets of Langerhans to secrete insulin. After sometime, due to constant stimulation, the beta cells get exhausted and lead to development of diabetes mellitus.
ii. Fat metabolism:
Acts on the adipose tissue. Neutral fats and triglycerides are broken down to release the free fatty acids. They are utilized for energy supply to the tissues.
This can lead to increased production of keto acids. Growth hormone also promotes the retention of sodium, potassium, calcium and phosphate since these substances are required for the growth of the body.
Regulation of Secretion of Growth Hormones:
It is mainly by the negative feedback control by the free form of the hormone level in circulation.
Growth hormone releasing hormone (GRH) secreted from the hypothalamus acts on anterior pituitary gland and stimulates the secretion of growth hormone, which in turn increases insulin-like growth factor (IGF) I or somatomedin C secretion from liver. When IGF I level in circulation increases, it acts on hypothalamus to stimulate the secretion of somatostatin (SS). SS on reaching anterior pituitary decreases the secretion of growth hormone (Fig. 6.12).
IGF I also acts directly on anterior pituitary and exerts inhibitory influence on the secretion of growth hormone.
GH secreted by the anterior pituitary gland is able to reach the hypothalamus through circulation and on reaching hypothalamus it stimulates the secretion of somatostatin. Somatostatin on reaching anterior pituitary inhibits further secretion of growth hormone.
Some of the other factors that increase the secretion of growth hormone are:
i. Increase in amino acids in circulation
iii. Free fatty acid decrease
v. At puberty
vi. Stage IV sleep.
The factors which inhibit the GH secretion are:
i. Dreaming or rapid eye movement (REM) sleep.
ii. Glucose increase.
Applied Aspects of Growth Hormones:
Deficiency of GH in children:
i. Hypothalamic dysfunction
ii. Pituitary destruction
iii. Defective GHRH receptor
iv. Biologically incompetent GH or GH receptor
v. Failure to produce IGF
vi. GH receptor deficiency
vii. GH receptor unresponsiveness: Laron dwarfism
i. It’s because of hyposecretion of GH from childhood.
ii. Person will have short stature. There will be a generalized stunted growth of the body.
iii. The person will have normal reproductive development.
iv. There will not be any mental abnormality and will have normal intelligent quotient (IQ).
v. Facial changes correspond with chronological age.
Achondroplasia is the most common form of dwarfism. The characteristic feature will be short limbs and normal trunk.
i. It will be due to insensitivity of the tissues to GH.
ii. The receptors are non-responsive to GH.
iii. There can be normal or elevated level of GH in circulation.
Deficiency of growth hormone in adult. The person appears older at an younger age.
Dwarfism could also be due to:
i. Cretinism—thyroxine deficiency
ii. Gonadal dysgenesis
iii. Kaspar Hauser syndrome—psychosocial dwarfism
iv. Achondroplasia—child born to aged father
Destructive disease of part of anterior pituitary. At times may include post-pituitary and hypothalamus.
i. Stunted growth.
iii. Decreased sexual development
v. Mentally subnormal
Deficiency of GH in adult:
i. Decreased muscle
ii. Decreased muscle strength and exercise performance
iii. Decreased lean body mass
iv. Decreased bone density
Acromegaly (Fig. 6.13):
i. Hypersecretion of growth hormone after the puberty.
ii. Enlargement of hand and feet (acral parts of the body only can grow because of the ossification of the long bones).
iii. There will also be enlargement of mandible which results in prognatism. There will also be enlargement and protrusion of frontal bone. Because of this, the person may have gorilla-like appearance.
iv. Certain osteoarthritic changes are also observed leading to kyphosis.
v. There can be enlargement of viscera especially that of heart and may lead to cardiomegaly.
vi. There can be hirsutism (increased hair growth on anterior part of trunk) and gynecomastia (enlargement of breasts even in males) and lactation (secretion of milk).
vii. The person may suffer from bitemporal hemianopia (a type of visual field defect) due to the compressing on the medial part of optic chiasma by enlarged pituitary gland.
i. Hypersecretion of hormone from childhood.
ii. Size of the person is pathologically big, but the person will be weak. Hence, the person is known as weak giant. There will not be proportionate growth of the contractile proteins in the muscles. Hence muscles are weak.
iii. The person is prone to develop early diabetes. This is because since growth hormone has hyperglycemic action, the sustained increase in blood glucose level may lead to exhaustion of beta cells of islets of Langerhans. So the person develops diabetes.
iv. The longevity of these people is restricted and die early.
i. Observed in female. Due to postpartum hemorrhage, there can be ischemic necrosis of pituitary gland.
ii. The pituitary gland secretion in general gets decreased.
iii. Symptoms include lethargy, sexually inactive, unable to withstand stress. Growth is inhibited and thyroid function is depressed.
iv. There can be atrophy of gonads. The menstrual cycle stops.
v. When there is general deficiency of all the hormones of anterior pituitary gland, this condition is known as panhypopituitarism.
It could be due to administration of dopamine antagonist/prolactin secreting adenomas.
c. Decreased libido
f. Testosterone level low