Growth hormone

Human Growth Hormone (hGH) is a polypeptide chain, composed of 191 amino acids and with a molecular mass of 21,500 Da. It is released by the anterior pituitary of both men and women. The secretion is stimulated 3 –4 hours after a meal, about 1 hour after the beginning of sleep, and after physical exercise. Hyposecretion of hGH becomes apparent in infants a few months after birth and may result in dwarfism. In the opposite case, hypersecretion of hGH results in gigantism and may be due to hypophysic tumors. In adults, when epiphyses are closed, hypersecretion of hGH provokes an increase in volume of soft tissues (hands, feet, lips), a proliferation of bones (acromegalysyndrome), and a limited tolerance of glucose Plays an important role in growth control.

Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues. Growth hormone secretion is regulated by three feedback loops, including both long, short and ultrashort loops. 1) GHRH inhibits its own secretion from the hypothalamus via an ultrashort- loop feedback. (2) Somatomedins, which are by-products of the growth hormone action on target tissues, inhibit secretion of growth hormone by the anterior pituitary. (3) Both growth hormone and somatomedins stimulate the secretion of somatostatin by the hypothalamus.

Growth hormone is secreted in a pulsatile pattern, with bursts of secretion occurring approximately every 2 hours. The largest secretory burst occurs within 1 hour of falling asleep (during sleep stages III and IV). The bursting pattern, in terms of both frequency and magnitude, is affected by several agents that alter the overall level of growth hormone secretion. The normal values often increase to as high as 50 ng/ml after depletion of the body stores of proteins or carbohydrates during prolonged starvation.

In brief, it has been found that growth hormone causes the liver (and, to a much less extent, other tissues) to form several small proteins called somatomedins that have the potent effect of increasing all aspects of bone growth. Many of the somatomedin effects on growth are similar to the effects of insulin on growth. Therefore, the somatomedins are also called insulin-like growth factors (IGFs). At least four somatomedins have been isolated, but by far the most important of these is somatomedin C (also called IGF-1).

The molecular weight of somatomedin C is about 7500, and its concentration in the plasma closely follows the rate of growth hormone secretion. Some aspects of the somatomedin hypothesis are still questionable. One possibility is that growth hormone can cause the formation of enough somatomedin C in the local tissue to cause local growth.

It is also possible that growth hormone itself is directly responsible for increased growth in some tissues and that the somatomedin mechanism is an alternative means of increasing growth but not always a necessary one Short Duration of Action of Growth Hormone but Prolonged Action of Somatomedin C. Growth hormone attaches only weakly to the plasma proteins in the blood. Therefore, it is released from the blood into the tissues rapidly, having a half-time in the blood of less than 20 minutes.

By contrast, somatomedin C attaches strongly to a carrier protein in the blood that, like somatomedin C, is produced in response to growth hormone. As a result, somatomedin C is released only slowly from the blood to the tissues, with a half- time of about 20 hours. This greatly prolongs the growth-promoting effects of the bursts of growth hormone secretion shown in Figure

The serum level of insulin-like growth factor-1 (IGF-1) and of its major circulating binding protein IGFBP-3 are types of these of biomarkers. They are used to diagnose and assess the degree of the human growth hormone (hGH)-deficient state, and to measure responsiveness and predict the outcome of hGH therapy of a patient. They are also used in the differential diagnosis of growth disorders in order to elucidate the etiology of the disease. In addition, IGF-1 and IGFBP-3, i.e. their ratio, can serve as safety biomarkers of hGH therapy.

IGF-1 measurement before and after growth hormone therapy.The Human Growth Hormone (hGH) ELISA is a solid phase sandwich ELISA method. The samples and anti-hGH-HRP conjugate are added to the wells coated with hGH MAb. hGH in the serum binds to anti-hGH MAb on the well and the anti -HGH second antibody then binds to hGH. Unbound protein and HRP conjugate are washed off by wash buffer. Upon the addition of the substrate, the intensity of color is proportional to the concentration of hGH in the samples. A standard curve is prepared relating color intensity to the concentration of the hGH.

The diagnosis of growth hormone defiance cant be made in a single random growth hormone level because growth hormone is secreted in pulses. Some pediatric endocrinologists diagnosis growth hormone defeciency based on an extremely low level of insuline like growth hormone which varies much less in the course of the day than growth hormone.

IGF1 levels are dependent on the amount of growth hormones in the blood but can also be low in normal, young children, so the test must be interpreted carefully. A more accurate but still imperfect way to diagnosis growth hormone deficiency is a growth hormone stimulation test. In this test, your child has a blood drawn for about 2 to 3 hours after being given medications to increase growth hormone release.

If the child does not produce enough growth hormone after this stimulation, then the child is diagnosed with growth hormone deficiency. However, growth hormone stimulation tests can over diagnose growth hormone deficiency. Growth hormone stimulation tests vary and are complicated, so they are usually performed under the guidance of a pediatric endocrinologist.

Usually, other tests to check the pituitary or to evaluate the brain MRI are performed when treatment is considered.

Clinical significant In children, ascertaining linear bone growth along the epiphyseal plate. Abnormally elevated levels lead to gigantism while complete absence slows the rate of growth one third to one half of normal. In adults, the epiphyseal growth plates ha fuse so hGH excess gradually produces acromegaly, a coarse thickening of the bones of the skull, hands and feet.

Growth hormone test The specimens shall be blood, serum in type and the usual precautions in the collection of venipuncture samples should be observed. For accurate comparison to established normal values a fasting morning serum sample should be obtained. The blood should be collected in a plain redtop venipuncture tube without anticoagulant or additive. Allow the blood to clot. Centrifuge the specimen to separate the serum from the cells.

Sample storage Samples may be refrigerated at 2-8 C for maximum period of five days. If the specimen can not assayed within this time, the samples may be stored at temperatures of -20C for up to 30 days. Avoid use of contamination devices. Avoid repetitive freezing and thawing. When assayed duplicate, ml of the specimen is required.

Principle In this method, GH calibrator, patient specimen or control is first added to streptavidin coated well. Biotinylated monoclonal and enzyme labeled antibodies(directed against district and different epitopes of GH) are added then the reactants mixed. Reaction between the various GH antibodies and native Gh forms a sandwich complex that binds with streptavidine coated to well.

After completion of the required incubation period, the enzyme-growth hormone antibody bound conjugate by aspiration or decantation. The activity of the enzyme present on the surface of the well is quantized by reaction with a suitable substrate to produce color.

Hyperglycemia inhibits growth hormone secretion. Age is an important factor in growth hormone concentrations. At birth, GH is high and generally declines with the exception of a burst during the growth phase of adolestronce. Women typically have a 50% higher level than their age- mached males.

normal Values