77. Growth hormone Flashcards
Growth hormone – GH
- In human - 191 amino acid long, single chain peptide.
- Produced by acidophil cells of the anterior lobe of the pituitary gland.
- Its synthesis shows both a short-duration and a long-duration.
- In the short run it shows a pulsating release, which occurs in every 20-30 minutes.
- Diurnal (day) plasma level of GH (in contrast with ACTH) is lower than the nocturnal (night) one. Its maximum level occurs within 3-4 hours after the onset of sleep. Its synthesis is under the influence of hypothalamic factors (GRH and GIF).
Growth hormone receptors
- Hormone-receptor complex
- It can be seen that after the hormone is bound to the receptor, a very conformational change (or energetical change) occurs on the intracellular side.
- This is able to start the activation of a second messenger system.
- The second messenger is the G-protein activated cAMP
Direct biological effects of GH
No action on endocrine glands, but on various organs or tissues.
- According to recent issues, it stimulates the secretion of further hormones (somatomedins) in the liver.
- Glandotropic and a histiotropic hormone.
GH effects
Increased growth hormone secretion;
-in young age = gigantism (significant increase of body measures compared with the average)
- in adult = acromegaly develops (acros= peak, megalo = big, giant). It means the asymmetrical growth of limbs, jaw, and certain flat bones.
- The epiphyses in certain species (e.g., the rat) do not close, therefore growth of rats can be continuously maintained by growth hormone.
- Decreased secretion during young life: dwarfism (nanosomia).
Episodic release of GH
- Analysis of continuously (day and night) taken blood samples shows that in young animals, an secretory peak appears within 3-5 hours after the onset of sleep
- No regular rhythm. The amplitude of this peak may reach the value that is 100-200 times higher than the diurnal level.
- Normal growth can not be maintained with high levels of GH, the precondition of normal body weight gain is the pulsatile increase and decrease of GH levels.
GH – protein metabolism
STH increases the uptake of amino acids in the cells and will by doing so increase the intracellular protein synthesis, this will increase growth. The production of STH will be directly stimulated by bringing free amino acids into the plasma. (especially arginine)
STH and GH is important anabolic hormones.
GH result in a positive nitrogen balance.
GH – protein metabolism - picture
GH – lipid metabolism
Effect of GH on adipose tissue is catabolic - lipolysis begins in adipose tissue. It mobilizes fatty deposits and increases plasma triglyceride and FFA levels.
This latter, and also amino acid incorporation increasing effects will stimulate glyconeogenesis.
In higher concentrations, it is ketogenic, because it stimulates the conversion of fatty acids into acetoacetic acid and beta-hydroxybutyric acid.
GH, therefore, mobilizes energy stores for the purpose of covering energy needs of enhanced protein synthesis.
GH – carbohydrate metabolism
- GH = diabetogenic hormone.
- It significantly increases plasma glucose level. As a consequence of enhanced serum FFA level, less glucose is taken up in muscle and adipose cells, glyconeogenesis is increased, more glucose is released from the liver.
- Finally, GH inhibits insulin-facilitated glucose uptake of adipose tissue, thus, increase plasma glucose level. The basic diabetogenic effects are correlated with the pancreatic glucagon synthesis stimulating effect of growth hormone.
- GH effectively stimulates glucagon production, therefore, overdosage of GH results in pathological hyperglycemia.
- The diabetogenic effect was first proven by Houssay in his classical experiment on dogs:
- If a dog was made diabetic by pancreatectomy, insulin deficiency hyperglycemia was developed.
GH – indirect effects
- Somatomedins, produced by the liver, have an influence on the bone, cartilage, and connective tissue.
- Their structure is similar to insulin therefore, they are also called IGFs (insulin-like growth factors). This peptide family consists of five peptide hormones, of which somatomedin C is outstanding and shown to be responsible for most of the effects. They circulate in the plasma, bound to carrier proteins. They cannot exert any effect on insulin receptors, since they cannot reach the appropriate concentration.
IGF-I effects
Stimulate:
-sulfate intake of chondrocytes – “sulfating factor”
- bone forming activity of chondrocytes and osteoblasts
- longitudinal bone growth
- transversal and periosteal bone growth
- bone growth in adults (acromegaly)
Acromegaly
Increased growth hormone secretion in adult individuals, where only periosteal bone formation is possible, acromegaly develops (akros= peak, megalo = big, giant). It means the asymmetrical growth of limbs, jaw, and certain flat bones. The epiphyses in certain species (e.g., the rat) do not close, therefore growth of rats can be continuously maintained by growth hormone.
Rat tibia test
- The rat is a “forever-young” animal, for its epiphyses do not close: it is always ready for growing.
- This is why rat tibia is very suitable for testing growth hormones. Rat tibia test is, as a matter of fact, a biological hormone- identification method.
- After administration of the unknown substance, the aim of the experiment is to test how thicker the tibial disk becomes compared with its previous, normal size.
- This method is so sensitive, that also quantitative determination of GH is possible with it, if plenty of GH is available. Nowadays, this method is certainly not used, because modern RIA (see also: Immunology) techniques make the exact quantification of nanograms of hormones possible.
Regulation of GH secretion
- Low glucose level and decreased level of arginine in the plasma will stimulate the secretion of growth hormone.
- At the same time, the presence of normal plasma level of thyroid hormone is ultimately important.
- Hormone synthesis and release are stimulated or inhibited by plasma hypothalamic factors according to actual needs. Adjustment of the average plasma concentration is a function of an endogenous hypothalamic signal generator. This page shows details of the regulation.
- The peripheral feedback system of the regulation consists of: plasma metabolite (glucose, arginine) levels, somatomedin (IGF) levels, and the plasma IGF-BP (IGF binding protein) concentrations (increases in the amount of the latter will decrease IGF uptake in hypothalamic- pituitary cells, thus, decreasing the efficiency of the feedback.
GH – practical approach
Growth hormone is suitable to increase productivity of the animals. This hormone, as already discussed, increases incorporation of valuable proteins by utilizing energy of fatty deposits.
- Application of growth hormone in livestock-breeding improves the utilization of foodstuff, increases milk production, improves the composition of body weight.
- Growth hormone may also be produced by genetic engineering technology.
