Human Growth Hormone Term Paper

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Human Growth Hormone in Biotechnology

Human growth hormone (GH), also known as somatotrophin, is a protein consisting of 191 amino acids with a molecular weight of ~22,000. Growth hormone is secreted by the pituitary gland, which stimulates growth and cell reproduction. The structure is made up of four helices, which are necessary for functional interaction with the GH receptor. Despite remarkable structural similarities between GH from different species, only human and primate GH may be active in humans.

History of Human Growth Hormone

Growth hormone was first purified from pig and cow pancreas for treatment of type 1 diabetes since the 1920's. However, these types of GH did not function as well in humans, due to greater variation of molecular structure compared to human GH. In 1958, Maurice Raben purified enough GH from human pituitary glands to successfully treat a GH-deficient boy (Raben). In 1960, the National Pituitary Agency was formed as a branch of the U.S. National Institutes of Health. The purpose of this agency was to supervise the collection of human pituitary glands after autopsy, arrange for large scale extraction and purification of GH, and distribute GH to a limited number of pediatric endocrinologists for treating GH-deficient children under research protocols.

Supplies of cadaveric GH were limited and only the most severely GH-deficient children were treated. From 1963 to 1985, ~7700 children in the U.S. And ~27,000 children worldwide were given GH extracted from human pituitary glands to treat severe GH deficiency. In 1976, physicians became aware that Creutzfeldt-Jacob disease may be transmitted by neurosurgical procedures and cornea transplantation. This disease is a rapidly fatal dementing disease of the brain also known as spongiform encephalopathy, related to "mad cow disease."

A shortage of available cadaver GH worsened in the late 1970's as the autopsy rate in the U.S. declined, while the number of pediatric endocrinologists able to diagnose and treat GH deficiency increased. However, in 1981, Genentech started trials of synthetic human GH made by recombinant DNA, in which human genes were inserted into bacteria so that bacteria could produce unlimited amounts of the protein.


In 1985, four young adults in the U.S. who had received growth hormone in the 1960's developed Creutzfeldt-Jacob disease (Frasier). The connection was recognized quickly and use of human pituitary GH ceased. Discontinuation of human cadaver growth hormone led to rapid Food and Drug Administration approval of Genentech's synthetic GH, which was introduced to the United States in 1985.

As of 2004, GH use continues to increase. Synthetic growth hormones available in the U.S. included Nutropin (Genentech), Humatrope (Lilly), Genotropin (Pfizer), Norditropin (Novo), and Saizen (Serono). The products are nearly identical in composition, efficacy, and cost, varying primarily in the formulations and delivery devices.

Functions of Human Growth Hormone

Growth hormone has an anabolic effect on the tissues of the body. One of the primary functions attributed to GH is height growth in childhood. This process is stimulated by two mechanisms. First, GH directly stimulates division and multiplication of chondrocytes of cartilage, which are the primary cells in the epiphyses of children's long bones. Second, GH stimulates production of insulin-like growth factor 1 (IGF1). The liver is a major target organ of GH for this process and is the principal site of IGF1 production. Insulin-like growth factor 1 has growth-stimulating effects on a wide variety of tissues.

In addition to height growth in childhood, GH serves many other metabolic functions. Growth hormone increases calcium retention, increases the mineralization of bone (Vestergaard and Mosekilde), increases muscle mass, induces protein synthesis and growth of many different organ systems of the body, resulting in a positive nitrogen balance.

Growth hormone also plays a role in metabolic homeostasis (Jorgensen et al.). Growth hormone reduces liver uptake of glucose, an effect that opposes that of insulin. Growth hormone also promotes lipolysis, which results in reduction of adipose tissue and free fatty acids and glycerol concentrations in the circulation......

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