growth hormone (GH) is a single polypeptide hormone which is produced and secreted by cells of the anterior pituitary gland. This hormone exerts diverse growth promoting and metabolic effects. As GH circulates in the blood, it binds to GH receptors (GHR), a trans membrane protein expressed on the surface of liver, adipose, kidney, heart, intestine, lung and muscle cells. After receptor binding, GH induces GHR dimerization and JAK2 is activated after its association with a dimerized GHR. A growth hormone antagonist (GHA) was produced in E.coli by a mutation that would block GH by preventing the GHR dimerization. In this study, we evaluated the effect of mutagenesis on binding energy of GH and GHA to their related receptor. The growth hormone and its mutant 3D structures were obtained from PDB (http://www.rcsb.org/pdb/home) and M4T server, respectively. Likewise, GHR conformational structure, was found in NCBI (http://www.ncbi.nlm.nih.gov). GH and GHA affinity for binding to GHR was analyzed by HEX docking software and energy total (E total) was obtained. GH and GHA E total were -648.13 and -698.68 respectively. This data demonstrates that GHA affinity for binding to GHR is higher than GH affinity. So GHA in completion to GH will overcome GH in binding to GHR, it can act as an antagonist to prevent excessive growth and cure acromegaly, diabetes and cancer.

Background: growth hormone (GH) produced by the somatotropic cells on the anterior part of the hypophysis.Its clinical application for many years was restricted to GH deficient children, but in recent years it has been widened to various other clinical conditions, not necessarily related to short stature. Currently, FDA has approved its usage in children with GH deficiency, Turner or Noonan syndromes, chronic renal failure, children born small for gestational age (SGA) and Prader-Willi syndrome. The aim of this paper was to summarize the current data on GH administration in modern pharmacotherapy.

There are numerous, often contradictory reports on the effect of growth hormone (GH) therapy on thyroid function. These reports prompted us to evaluate the impact of GH therapy on thyroid function in previously euthyroid children with GH deficiency. Twenty five clinically and biochemically euthyroid children with GH deficiency were studied. A thyroid profile (T4, Free T4, T3 and TSH) was performed at baseline and 3, 6 and 12 months after GH therapy in 21 children with idiopathic growth hormone deficiency (group A) and 4 children with organic GH deficiency (group B). We observed a significant reduction in serum T4 and free T4 concentrations during GH therapy in both groups (P<0.01). No patient in group A had free T4 levels fell into the hypothyroid range, while in one of four patients in group B, free T4 value fell into the hypothyroid range during GH therapy. In both groups, no significant variation in serum TSH and T3 was recorded at any time. Our data suggest that GH therapy can introduce changes in thyroid function and so confirm the need of a careful monitoring of thyroid function in particular in children with organic GH deficiency during long-term GH therapy.

Background: Insulin-like growth factor-1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) are used widely for evaluating growth hormone deficiency (GHD). We evaluated the effect of recombinant human growth hormone treatment on serum IGF-1 concentrations in Indian children with GHD over a period of 24 months. Patients and Methods: Patients who presented with short stature were evaluated. The enrolled subjects exhibited a height standard deviation score (SDS) of less than-3 and/ or a height velocity SDS of less than-2 over a 12-month period, and they displayed GH concentrations of less than 10 ng/ml in 2 provocative tests. Patients received a detailed physical examination that included auxology, pubertal staging, and biochemical assays to measure IGF-1 concentration. All patients received GH at a dose of 0.3 mg/kg/week in 7 divided doses subcutaneously daily at night. Patients with multiple pituitary hormone deficiencies received additional substitution therapy. Results: Twenty-five prepubescent children (male: female=14:11) at a mean age of 8.6±2.9 years were enrolled. The height SDS at baseline, 1 year, and 2 years was -5.38±1.4, -4.10±1.4, and -3.6±1.3, respectively (P<0.005), whereas the IGF-1 SDS at baseline, 1 year, and 2 years was -3.40±0.8, -1.74±1.2 and, -1.54±1.7, respectively (P>0.1). No significant difference in height change SDS was detected between children with an IGF-1 SDS in the normal range and children with an IGF-1 SDS of less than -2 at 2 years. Bone age advancement, the occurrence of puberty, and levels of fasting glucose and HbA1C did not change during therapy. Conclusions: Our study on Indian children indicates that changes in serum IGF-1 SDS concentrations may not be a reliable marker for responsiveness to GH therapy.