Human growth hormone College of Dentistry Dr Mouaadh Abdelkarim

somatotropic or somatotropin Polypeptide 191 amino acid residues MW = daltons Highly hydrophobic proteins

In contrast to other hormones, growth hormone does not function through a target gland but exerts its effects directly on all or almost all tissues of the body. Somatotrophs

Growth hormone promotes growth of many body cells Promote increased size of the cells Increased mitosis Specific differentiation of certains types of cells such as bone growth cells and early muscle cells

Growth hormone has several metabolic effects 1- Increased rate of proteins synthesis in most cells of the body 2- Increased mobilization of fatty acids from adipose tissue, increased free fatty acid in the blood, and increased use of fatty acids for energy. 3- Decreased rate of glucose utilization through the body

1- Increased rate of proteins synthesis in most cells of the body (anabolic effect) GH promotes protein deposition in tissues : >> enhancement of amino acid transport through the cell membrane >> enhancement of RNA translation to cause protein synthesis by the ribosomes >> Increased nuclear transcription of DNA to form RNA >> Decreased catabolism of protein and amino acids

2- increased mobilization of fatty acids. >>> release of fatty acids from adipose tissue >>>increasing the FFA in the body fluids >>> conversing of FFA to acetyl coenzyme A >>> fat is used for energy in preference to the use of carbohydrates and proteins. >>> ++GH>> +++ acetoacetic formed by the liver>>> causing ketosis>>>fatty liver.

3- decreased rate of glucose utilization through the body (decrease carbohydrate utilization) Decreased glucose uptake in tissues such as skeletal muscle and fat (anti-insulin effect) Increased glucose production by the liver increased insulin secretion (cause insulin resistance). Excess secretion of growth hormone =metabolic disturbances very similar to patients with type II diabetes. (diabetogenic effect)

Necessity of insulin and carbohydrate for the growth promoting action of growth hormone Animal +lacks of pancreas>>>>no growth hormone effect Animal+ diet without carbohydrate >>>> no growth hormone effect Carbohydrate and insulin>>production of energy Insulin : transport of amino acids into cells and glucose transport stimulation

Growth hormone stimulates cartilage and bone Growth Increased deposition of protein by the chondrocytic (cartilage) and osteogenic (bone) cells that cause bone growth Increased rate of reproduction of these cells Converting chondrocytes into osteogenic cells, that causing deposition of new bone

Somatomedins (insulin Like Growth factor) Chondrocytes cultured outside the body+ growth hormone= proliferation or enlargement fails. Growth hormone +inside body= proliferation and growth of cells >>>>>>>>>>>> cofactor ????

Growth factor>>induce liver and other tissues to produce somatomedins (Somatomedins are a group of hormones that promote cell growth and division in response to stimulation by growth hormone).hormones Somatomedin have similar effect with insulin>>>>insulin like growth factors (IGFs) 4 somatomedin…somatomedin C (IGF-I)

Half time of GH: 20 minutes Half times of somatomedin C : 20 Hours Prolongs the growth promoting effects of the bursts of growth hormone.

Regulation of growth hormone secretion Adolescence>>>>>adult: decrease by 75% of GH [] Stimulate growth hormone: decreased blood glucose decreased FFA fasting, starving, protein deficiency trauma, stress, excitement Exercise Testosterone Deep sleep GHRH Inhibit growth hormone: increased blood glucose increased FFA Aging Obesity Somatostatin (GHIH, SRIF) Somatomedins

Control of Growth Hormone secretion GHIH = Somatotropin Release-Inhibiting Factor

GH Disorders GH excess Before puberty – results in gigantism Epiphyseal growth plates have not closed, so, long bones of arms and legs increase in length After puberty – results in acromegaly Epiphyseal growth plates already closed, so, long bones don’t lengthen; rather bones tend to increase in diameter instead, especially prominent in bones of face and hands GH deficiency Results in dwarfism

Pygmies of Africa>>>inability to synthesize significant amount of somatomedin C despite GH [] NORMAL Lorain-Levi dwarfism (mutations in the gene for the GH receptor.)mutations

GiganitsmAcromegalyDwarfism