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Growth Hormone (hGH) . Somatotropin Small protein expressed from anterior lobe of pituitary produced by Somatotroph cells of the anterior pituitary Growth hormone (hGH) is a peptide hormone Essential for normal development Promotes growth, especially in children and at puberty 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 of fat. Somatic growth hGH stimulates linear bone growth primarily by increasing amino acid uptake and protein synthesis in (bone cells). It acts indirectly through stimulating the synthesis of somatomedins ( insulin-like growth factors (IGF) by the liver cause secretion of collagen and minerals necessary for cartilage and bone growth. hGH causes an increase in organ size and function. It promotes both increased sizes of cells and increased mitosis, with development of increased numbers of cells. Non-Growth Actions of hGH hGH also has direct actions on fat cells, liver and muscles which are not growth promoting but are metabolic in function. It causes the breakdown of fat - Increased rate of protein synthesis in all cells of the body t stimulates glucose produced by gluconeogenesis bringing about a rise in plasma glucose. - Effect Metabolism Effect on CHO and fat metabolism (Diabetogenic) The effect of hGH on metabolism is to increase the energy substrates, glucose and free fatty acids, The effect of hGH on increasing serum glucose levels is two-fold glucose uptake by muscle and adipocytes is decreased. glucose synthesis (gluconeogenesis) by the liver is stimulated. Effect Metabolism (cont..) Effect on Fat Metabolism Causes Insulin Resistance hGH decreases body fat by increasing lipolysis in adipose tissue leading to decreased fat storage and increased FFA concentration in circulation i.e. it causes mobilization of fats. The result is decreased fat storage - High blood glucose& fatty acids causes Insulin Resistance Effect on protein and electrolyte metabolism (Protein Sparing) Growth hormone is a protein anabolic hormone Increase in lean body mass and a decrease in body fat along with an increase in metabolic rate and in serum cholesterol Effect on Tissues The mediators of hGH action are called insulin-like growth factors (IGF) or Somatomedins which are produced by the liver In addition, hGH increases lean body mass through the increase of muscle protein synthesis. -Size of internal organs also increased Following puberty, hGH levels decline during adulthood and decrease further with aging. 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 (GHRH) and Growth hormone inhibitory hormone (GHIH or Somatostatin). Both act on the anterior pituitary to stimulate or inhibit the production of growth hormone. = Somatostatin (GHIH) = Somatomedin-C Regulation of release of growth hormone The regulation of the ‘HYPOTHALAMIC –PITUITARY axis’ is by IGF-1, which acts on the hypothalamus to inhibit GHRH and stimulate Somatostatin or (GHIH). Circulates in the blood tightly bound to a large plasma protein. Has a long half-life. The levels of hGH rise during sleep, in adults as well as children. Excess and deficiency of HGH Excess HGH The most common cause of excess is a pituitary tumor. 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. Giagantism Due to tumour in the cells secreting growth hormone in the anterior pituitary. -Increased secretion of growth hormone before adolescence (before union of the ends of the bones with the shafts (bone maturation). -The giant becomes longer than usual) more than 2 meters length -Muscles may be well developed but later undergo some atrophy and weakening. -The life span is shorter than normal Acromegaly An excessive production of growth hormone in an adult results in enlargement of skeletal extremities. For instance, the flat bones and soft tissues of the hands, feet, face,nose (acromegalic facies) and lower jaw (prognathism) and forehead become enlarged and the skin becomes coarse. Growth hormone can also stimulate the growth of connective tissue such as ligaments, capsules and synovial membranes. Another condition commonly associated with Acromegaly is diabetes mellitus. As growth hormone causes tissue resistance to insulin and is therefore Diabetogenic. -liver, kidney, spleen becomes larger than normal Growth hormone deficiency (Dwarfism) the child becomes shorter than normal -Occurs when growth hormone decreases or become absent in childhood and before adolescence In adults a growth hormone deficiency is not a major problem and is very treatable