Slide 1: Small protein (191 amino acids) expressed from anterior lobe of pituitary produced by somatotroph cells of the anterior pituitary
Growth hormone (GH) is a peptide hormone
Essential for normal development
Promotes growth, especially in children and at puberty Growth Hormone (GH)
A.K.A. Somatotropin Hypothalamus –ant pituitary : Hypothalamus –ant pituitary The synthesis and release of GH is under the control of the hypothalamic hormones
The hypothalamus produces a pair of hormones, growth hormone releasing hormone (GRH) and
Growth hormone inhibitory hormone (GIH or somatostatin).
Both act on the anterior pituitary to stimulate or inhibit the production of growth hormone (or human growth
hormone) (HGH) or Somatotrophin CONTROL OF GROWTH HORMONE SECRETION : CONTROL OF GROWTH HORMONE SECRETION Slide 4: Under normal conditions GH is secreted episodically at 2-hour intervals.
These surges can be influenced by other physiological stimuli.
Fall in circulating levels of energy substrates (free fatty acids or glucose)
an increase in protein or amino acid levels can stimulate GH secretion.
Exercise or certain stresses (fever, trauma, or surgery) also stimulate GH release.
A peak in GH secretion is also seen 1 hour after the onset of deep sleep (stage 3 or 4). Slide 5: Secretion is pulsatile mainly during the night
Pulses more frequent in pubertal adolescents
Facilitated by the pubertal increase in androgen
Secretion of GH requires the presence of
normal plasma levels of thyroid hormone
During the sixth decade secretion diminishes
considerably in both men and women Indirect actions of HGH : Indirect actions of HGH The effect of HGH on the liver is to produce a number of somatomedins or growth factors now usually called insulin-like growth factors – IGFs.
The actions of HGH are mediated mainly through IGF-1, the effects of which are to stimulate growth in bone, protein synthesis in muscle and lipolysis in fat. Direct actions of HGH : Direct actions of HGH HGH also has direct actions on fat cells and liver and muscle which are not growth promoting.
In fact, they are sometimes referred to as anti-insulin or diabetogenic effects.
It causes the breakdown of both fat and muscle, the resulting glucose produced by gluconeogenesis bringing about a rise in plasma glucose. Regulation of release of growthhormone : Regulation of release of growthhormone The regulation of the ‘axis’ is by IGF-1, which acts on the hypothalamus to inhibit GRH and stimulate somatostatin.
Circulates in the blood tightly bound to a large protein
Has a long half-life
Plasma IGF-I serves as a reflection of 24-hour GH secretion
The levels of HGH rise early in sleep, in adults as well as children. Somatic growth : Somatic growth GH stimulates linear bone growth primarily by increasing amino acid uptake and protein synthesis in chondrocytes (bone cells).
GH causes an increase in organ size and function. Slide 11: In addition, GH increases lean body mass through the increase of muscle protein synthesis.
Following puberty, GH levels decline during adulthood and decrease further with aging.
Decline in lean body mass and metabolic rate as well as increased adipose tissue associated with aging may be attributed to declining GH levels Effect on body metabolism Effect on carbohydrate and fat metabolism : Effect on body metabolism Effect on carbohydrate and fat metabolism Overall, the effect of GH on metabolism is to increase the energy substrates, glucose and free fatty acids, while stimulating protein synthesis in muscle.
The effect of GH on increasing serum glucose levels is two-fold – glucose uptake by muscle and adipocytes is decreased while glucose synthesis (gluconeogenesis) by the liver is stimulated.
Finally, GH decreases body fat by increasing lipolysis in adipose tissue leading to decreased fat storage.
The result is decreased fat storage an increase in lean body mass. Effect on protein and electrolyte metabolism : Effect on protein and electrolyte metabolism Growth hormone is a protein anabolic hormone and produces a positive nitrogen balance, a fall in the blood urea nitrogen and amino acids levels.
Increase in lean body mass and a decrease in body fat along with an increase in metabolic rate in plasma cholesterol Effect on the tissues : Effect on the tissues In most tissues, the effect of GH is not direct.
That is, GH must stimulate the production of another factor that mediates the physiological effects of GH.
The mediators of GH action are called insulin-like growth factors (IGF) or sommatomedins.
These factors, which are produced by the liver in response to GH, can act on multiple tissues to regulate their growth and/or function.
The majority of GH effects are mediated by IGF production Excess and deficiency of HGHExcess HGH : Excess and deficiency of HGHExcess HGH The most common cause of excess is a pituitary tumour.
In children who are still growing, excess HGH causes gigantism.
In adults whose long bones can no longer be extended, the condition is known as acromegaly. Acromegaly : Acromegaly An excessive production of growth hormone in an adult results in enlargement of skeletal extremities.
For instance, the bones and soft tissues of the hands, feet, face (acromegalic facies) and lower jaw (prognathism) become enlarged and the skin becomes coarse.
Growth hormone can also stimulate the growth of connective tissue such as ligaments, capsules and synovial membranes.
A combination of connective tissue growth and hypertrophied bones compresses the local nerves causing pain, burning sensation in the joints, stiffness in the limbs, and tingling and numbness in the hands
Another condition commonly associated with acromegaly is diabetes mellitus. It affects, to some extent, up to 25% of people with acromegaly because growth hormone causes tissue resistance to insulin. Gigantism : Gigantism In gigantism, growth is gradual but continuous and consistent; the affected person, with bones in normal proportion, may attain a height of 8 feet.
Muscles may be well developed but later undergo some atrophy and weakening.
The life span is shorter than normal Growth hormone deficiency : Growth hormone deficiency Prepuberty results in dwarfism
Normal growth hormone but decreased IGF-I prepuberty results in Laronsyndrome
In adults a growth hormone deficiency is not a major problem and is very treatable