Recombinant Human Growth Hormone and GH Deficiency

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admin | Apr 18, 2010 | 0 comments
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Growth hormone (GH) is species-specific, and humans do not respond to GH derived from animals. In the past, the only human GH available for treating children who were GH-deficient was very limited mount made from human pituitaries obtained at autopsy, but there was never enough to meet the need. This problem was solved when the gene for human GH was cloned in 1979 and then expressed in bacteria. The production of large amounts of recombinant human GH, with all the activities of the natural substance, was now possible. During the 1980s, careful clinical trials established that recombinant human GH was safe to use in GH-deficient children to promote growth. The hormone was approved for clinical use and is now produced and sold worldwide.

Despite the availability of recombinant GH, the diagnosis of GH deficiency has remained controversial. GH is released in periodic bursts, the greatest of which occur in the early morning hours. Between pulses of secretion, the blood concentration of GH is nearly undetectable by most techniques. For these reasons, a random measure of GH in the blood is not useful for diagnosing GH deficiency. However a random blood sample may be useful to detect GH resistance, a syndrome in which the patient exhibits symptoms of GH deficiency but presents with high GH levels in the blood.

An alternative means of diagnosing GH deficiency is to measure the levels of IGF-1, IGF-2, and the IGF-binding protein 3(IGFBP3) in the blood. The IGFs mediate many of the mitogenic effects of GH on tissues in the body. IGF-1 and IGF-2 bind to IGFBP3 in the blood. IGFBP3 extends the half-life of the IGFs, transports them to target cells, and facilitates their interaction with IGF receptors. GH stimulates the production of all three molecules, which are present in the blood at fairly constant, readily detectable levels in normal individuals. In children with GH deficiency, the concentration of IGFs and IGFBP3 are low. Treatment with recombinant GH will increase IGF-1, IGF-2, and IGFBP3 in the blood, which will result in increased long bone growth. The epiphyseal growth plate in the bone becomes less responsive to GH and IGF-1 several years after puberty, and long bone growth stops in adulthood.

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