Human Growth Hormone (HGH) Research & Studies

The minigene encoding human growth hormone (hGH) has been incorporated into over 300 transgenic mouse lines to improve transgene expression. However, unexpected and functional hGH expression can drastically alter physiology. We list here the mouse lines in which ectopic hGH has been confirmed, and we provide a wiki for lines awaiting analysis.

The evaluation of clinical and analytical parameters as predictors of the final growth response in Turner syndrome patients treated with growth hormone.

Growth hormone (GH) structure is stabilised by two disulphide bonds, C53-C165 and C182-C189 in human GH. Researchers have investigatedthe role of these structural features since the late 1960s. Early studies implied that the disulphide bonds would not be importantfor biological activity of GH. However, more advanced techniques, as well as clues from patients carrying mutations in their GH1 gene,have demonstrated that the integrity of the disulphide bond between cysteines C53 and C165 is required for biological activity of GH.In contrast, disruption of the C-terminal disulphide bond (C182-C189) has only modest effects on the biological potency of GH, despitedecreased binding affinity to GH receptor and reduced stability as shown by a comprehensive in vitro study.To confirm these results, we generated transgenic mice that express a human GH analogue, C189A, and observed normal growth-promotingand lipolytic activities. In this article, we present new data and review old results concerning the disulphide bonds of GH. We also discussrelevant mutations found in patients with growth disorders.

With an increasing spectrum of indications for growth hormone (GH), knowledge of the short- and long-term safety of this treatment is essential. In this chapter we review the main adverse effects that have been demonstrated or discussed after long-term GH treatment in children. It is well recognized that plasma insulin concentrations increase during GH treatment. The incidence of type 2 diabetes is raised during GH treatment, especially in subjects with other risk factors. Recommendations include assessing glucose tolerance by measuring plasma glucose and HbA1c before and during treatment. There is no consensus on the indications for insulin measurement and/or oral glucose tolerance tests. Other recognized short-term complications of GH treatment include pseudo-tumour cerebri, otitis media (Turner syndrome), and orthopaedic problems such as worsening of scoliosis and slipped femoral epiphysis. There are reports of sudden death within the first 6 months of treatment in children with Prader-Willi syndrome, mostly associated with severe obesity. Large cohort follow-up studies suggest that children treated with GH following childhood cancer treatment do not have a greater number of relapses, but there may be a higher incidence of second primary tumours in the early years of GH therapy. A cohort treated with human pituitary GH showed a higher incidence of tumours, and a GH effect on tumorigenesis has been seen in follow-up studies of acromegaly raising the question of whether de novo cancer risk may be increased. A new prospective pan-European safety surveillance study (SAGhE) has been launched to address these essential questions. The role of monitoring the IGF-1 response (total or free concentrations) to GH treatment to predict long-term safety is unclear at present. Attempts to target IGF-1 levels within the normal range may result in the use of excessive doses of GH. In general, higher dosage GH regimens may be associated with supraphysiological IGF-1 levels.

Human growth hormone (GH) has a number of accepted medical uses, but has quickly become a popular ergogenic aid among athletes. The issue of performance-enhancing substances such as anabolic steroids and GH has drawn the attention of athletes, their parents, and politicians. On almost a daily basis, headlines about the status of doping in professional, international, and amateur sports seem to be more pervasive. The supraphysiologic effects of GH lead to lipolysis, with increased muscle volume. Due to the ethical limitations of studying the use of high doses of GH in isolation or combined with anabolic steroids, the scientific literature has not produced compelling results on its efficacy. GH has potential as an anti-aging drug and does lead to some improved athletic performance in isolated studies. Despite the lack of compelling data, GH seems to have developed a reputation among athletes for enhancing performance. The detection of illegal doping with GH has been the focus of a concerted international effort by the International Olympic Committee. A number of promising detection techniques may allow the detection of illicit GH use. This review on GH as an ergogenic aid includes a discussion of the basic physiology of GH and its actions, the accepted medical indications for its use, the results of scientific studies that assess whether it improves exercise performance or work capacity, and the scientific techniques under development to detect ergogenics with strong abuse potential.

The Food and Drug Administration has approved a treatment IND allowing Serono Laboratories to distribute its experimental version of human growth hormone (HGH) to people with AIDS-related wasting syndrome. To receive HGH, a person with AIDS must have lost 10 percent of normal body weight without apparent cause, and must have first tried the appetite stimulants Megace and Marinol. HGH reorients the body's metabolism so that is focuses on rebuilding protein stores that are lost from lean tissue mass during the course of the disease. Wasting can be either acute and caused by a specific gastrointestinal or other infection, or chronic and non- specific. The treatment IND covers 12 weeks of therapy during which physicians will examine their patients 4 times and collect basic safety data for Serono. Patients can be reenrolled for an additional 12 weeks if a need for HGH remains. Patients or third- party payers will have to reimburse doctors for data collection and paper work costs, and will pay $25 per mg (a daily dose is 6 mg). This cost recovery is a precedent-setting aspect of Serono's treatment IND.

This review has attempted to answer a number of questions regarding human growth hormone therapy in growth hormone deficiency. I believe that the available data support several conclusions which form a suggested current approach to the clinical use of hGH. While these conclusions are derived from data obtained using pituitary growth hormone, it is likely that they are applicable to growth hormone manufactured by recombinant DNA technology, as well. Treatment should be begun as early as the diagnosis can be made in anticipation of a better initial and long-term response in younger patients. Growth hormone should be administered on the basis of body weight in an initial dose of 0.06-0.10 unit/kg 3 times a week. Growth hormone may be administered either intramuscularly or subcutaneously. Therapy should be continuous whenever possible. Treatment should be given until there is no further response which generally will reflect closure of the epiphyses. Associated hormone deficiencies should be adequately treated, and patients should be periodically evaluated for the development of additional deficiencies. Concomitant therapy is not indicated unless deficiencies are clearly demonstrated. Thyroid replacement should be at full dosage, while glucocorticoid replacement should probably not exceed 10-15 mg/m2 x day. Gonadal steroids should be used at the bone age when puberty is expected, and hGH should be continued during pubertal development. There is no general indication for giving anabolic/androgenic steroid in combination with hGH in prepubertal patients. If a waning effect of therapy is observed, the dose of hGH should be incrementally increased, and/or the addition of anabolic/androgenic steroid therapy should be considered. While most reports have focused on the effect of hGH on linear growth, changes in weight, bone age, body proportions, and body composition have also been observed. The effect on bone age is variable, but there is greater enhancement of linear growth than of epiphyseal development in the majority of treated patients. Bone age must be monitored during hGH administration whether or not anabolic/androgenic steroids are used concurrently. Growth hormone administration is remarkably free of side effects. However, neutralizing antibodies to hGH may develop and they should be sought in patients in whom an unexplained decrease in response is observed. Certainly the available incomplete data allow for different conclusions. The expanding supply of hGH should lead to a more systematic evaluation and provide more definite answers to the questions which this review has considered.

Chemical investigations of the human growth hormone (HGH) molecule were briefly reviewed for th period between 1974 and 1981. These include chemical modification, selective enzymic cleavage, the 20K HGH, synthetic peptide fragments, complementation of the natural NH2-terminal 134-amino acid fragment with natural or synthetic COOH-terminal fragments of various chain lengths, covalent reconstitution of two contiguous fragments of HGH with thrombin and bacterially synthesized methionyl-HGH.