Growth hormone and biotechnology BY Esteftah Mohamed El-Komey

Growth hormone Growth hormone (GH or somatotropin) is a 191 amino acid and a molecular weight of about 22,000 daltons. , single chain polypeptide hormone which is synthesised, stored and secreted by the stomatotraph cells within the lateral wings of the anterior pituitary gland, which stimulates growth and cell reproduction in humans and other vertebrate animals.

A polypeptide hormone secreted by the anterior lobe of the pituitary gland that promotes growth of the body, especially by stimulating release of somatomedin, and that influences the metabolism of proteins, carbohydrates, and lipids. Also called human growth hormone, somatotropic hormone; Also called somatotropin.

A deficiency of growth hormone secretion before puberty (by the end of which the synthesis of new bone tissue is complete) results in pituitary dwarfism. Pituitary dwarfs, who can be as little as 3 to 4 ft (91–122 cm) tall They can be treated by injections of synthetic growth hormone, either somatrem or somatropin, which are produced by genetically engineered bacteria. The genes for human growth hormone are localized in the q22-24 region of chromosome 17 In 1985, biosynthetic human growth hormone replaced pituitary-derived human growth hormone for therapeutic use in the U.S. and elsewhere. Biosynthetic human growth hormone, also referred to as recombinant human growth hormone, is also called somatropin and abbreviated as rhGH. Since the mid-1990s the abbreviation HGH has begun to carry paradoxical connotations, and now rarely refers to real GH used for indicated purposes.

Functions of GH It promotes lipolysis, which results in the reduction of adipose tissue (body fat). GH directly stimulates division and multiplication of the primary cells in the growing ends of children's long bones (arms, legs, digits). GH also stimulates production of insulin-like growth factor 1 (IGF1 Other functions It increases calcium retention, and strengthens and increases the mineralization of bone It increases muscle mass through the creation of new muscle cells

Functions of GH It increases protein synthesis and stimulates the growth of all internal organs excluding the brain. It plays a role in fuel homeostasis. It reduces liver uptake of glucose, an effect that opposes that of insulin. It also contributes to the maintenance and function of pancreatic islets. It stimulates the immune system.

I. What is biotechnology? Biotechnology is The application of biological knowledge and techniques to develop products or solve problems Molecular biotechnology. Employs the tools of molecular biology (recombinant DNA, gene cloning) to engineer the genetic information/blueprint of living organisms to produce useful, marketable products.

Recombinant Protein Technologies Recombinant protein: Any protein produced by any kind of cellular machinery derived from an expression system (plasmid, viral) (in vivo - whole organisms, in vitro - in cells) Benefits of Recombinant Proteins One of the greatest benefits of recombinant proteins is that they can be produced in greater quantities than are available from natural sources. This is particularly true if the protein comes from a rare, endangered or particularly valuable species.

Clinical problems: too much and too little Growth hormone excess: (acromegaly and pituitary gigantism) Growth hormone deficiency (GHD) Deficiency of GH produces significantly different problems at various ages. In children, growth failure and short stature are the major manifestations of GH deficiency. In adults the effects of deficiency are more subtle, and may include deficiencies of strength, energy, and bone mass, as well as increased cardiovascular risk. GH deficiency is treated by replacing GH. All GH in current use is a biosynthetic version of human GH, manufactured by recombinant DNA technology. As GH is a large protein molecule, it must be injected into subcutaneous tissue (or muscle) to get it into the blood.

The Future for Growth Hormone In years past, growth hormone purified from human cadaver pituitaries was used to treat children with severe growth retardation. In contrast to insulin, porcine and bovine pituitary growth hormones don’t work in humans. Only growth hormones from humans or from closely related primates will function in humans. Genetic engineering means that there is a plentiful supply of growth hormone for everyone who needs it. Growth hormone might have a role in anti-aging treatments and this is being researched at present. The cow version, bovine growth hormone, and the pig version, porcine growth hormone, have been used in animals to increase yields of milk and of leaner meat without any harmful effects on humans who eat the

Biotechnology and Recombinant DNA

1. Creating Recombinant DNA

2. Inserting vectors into host cells

3. Selecting transgenic cells

Dwarfism is a term applied broadly to a number of conditions resulting in unusually short stature. More than 150,000 children in the United States receive growth hormone therapy to remedy growth retardation caused by endocrine deficiencies.

Figure 3 Promoter function seen in transgenic mice Figure 3   Promoter function seen in transgenic mice. (A) Recombinant plasmid containing rat growth hormone structural gene, mouse metallothionein regulatory region, and bacterial plasmid pBR322. The plasmid, pMGH, was injected into the mouse oocytes. The dark boxes on the injected plasmid correspond to the exons of the GH gene. The direction of transcription is indicated by an arrow. (B) A mouse derived from the eggs injected with pMGH (left) and a normal littermate (right). (From Palmiter et al. 1982, photograph courtesy of R. L. Brinster.)