Human Growth and Growth Hormone: From Antiquity to the Recominant Age to the Future

Abstract

Since antiquity Man has been fascinated by the variations in human (and animal) growth. Stories and art abound about giants and little people. Modern genetics have solved some of etiologies at both extremes of growth. Serious study began with the pathophysiology of acromegaly followed by early attempts at treatment culminating in modern endoscopic surgery and multiple pharmacologic agents. Virtually at the same time experiments with the removal of the pituitary from laboratory animals noted the slowing or stopping of linear growth and then over a few decades the extraction and purification of a protein within the anterior pituitary that restored, partially or in full, the animal’s growth. Human growth hormone was purified decades after those from large animals and it was noted that it was species specific, that is, only primate growth hormone was metabolically active in primates. That was quite unlike the beef and pork insulins which revolutionized the care of children with diabetes mellitus. A number of studies included mild enzymatic digestion of beef growth hormone to determine if those “cores” had biologic activity in primates and man. Tantalizing data showed minimal but variable metabolic efficacy leading to the “active core” hypothesis, for these smaller peptides would be amenable to peptide synthesis in the time before recombinant DNA. Recombinant DNA changed the landscape remarkably promising nearly unlimited quantities of metabolically active hormone. Eight indications for therapeutic use have been approved by the Food and Drug Administration and a large number of clinical trials have been undertaken in multiple other conditions for which short stature in childhood is a sign. The future predicts other clinical indications for growth hormone therapy (and perhaps other components of the GH?IGF-1 axis), longer-acting analogues and perhaps a more physiologic method of administration as virtually all methods at present are far from physiologic.

Insights into Pathogenesis, Nutritional and Drug Approach in Sarcopenia: A Systematic Review

“…Although in recent years, the recombinant human GH (rHGH) has become a target of abuse in the community of competitive sports, the variations in human and animal growth have awakened scientists' attention. As it is also related to muscle development, GH emerged as a potential therapeutic against sarcopenia [133,134]. The GH depends on its carrier insulin-like growth factor (IGF-1) to act physiologically and therapeutically.…”

Growth and Growth Hormone through the Ages: Art and Science

“…The support and lobbying from parent groups were important for several of these indications. The studies that led to the approvals have been reviewed recently [95] and there are extensive published reviews for each of these conditions as well as reports of clinical trials for other conditions for which hGH has not yet been approved, e.g., children with cystic fibrosis, achondroplasia and X-linked hypophosphatemia (XLH) [95].…”

Non-Covalent Albumin Ligands in FDA-Approved Therapeutic Peptides and Proteins

“…Between 1961 and 1985, only cadaveric HGH was available for therapy, but this practice was stopped after cases of Creutzfeldt–Jacob disease. In 1985, the FDA finally approved recombinant HGH from Genentech …”