Assignment 1

Growth Hormone

Growth hormone, is a peptide hormone that is synthesized in the anterior pituitary. In mammals, growth hormone promotes an increase in body weight and height, skeletal growth, muscle growth and increase in cell size and numbers. In rodents, it also accounts for increased tail length. Growth hormone induces growth in invertebrates as well as vertebrates. In humans, the presence of growth hormone is greatest immediately following birth, and during puberty at which times there is a high amount of rapid growth.

Figure 1: 3D Structure of Growth Hormone

Structure

Growth hormone is a single-chain polypeptide of 191 amino acids, and a molecular weight of approximately 22 kD in most species. Two disulfide bonds exist in the structure between Cys53 and Cys165, and between Cys182 and Cys189. There are many forms of growth hormone other than the 22kD version (which accounts for approximately 70% of variants). A 20kD version exists as well as numerous dimers and polymers.

Figure 2: Structure of Growth Hormone

Synthesis and Release

Growth hormone synthesis is affected by various factors including stress, exercise, nutrition, sleep etc. However, its primary controllers are growth hormone releasing hormone (GHRH), somatostatin (SS) and Ghrelin. GHRH stimulates both the synthesis and secretion of growth hormone, while somatostatin inhibits the release of GH. Ghrelin also stimulates GH release. The hypothalamus secretes GHRH, which acts on the pituitary, which releases GH. Ghrelin is released from the stomach, acts upon the pituitary, releasing GH. When the hypothalamus secretes somatostatin, it inhibits GHRH from acting upon the pituitary, as well, it inhibits the stomach from releasing ghrelin and the pituitary from releasing GH.

Growth hormone also stimulates the production of insulin-like growth factor 1 (IGF1) by the liver. Both GH and IGF1 are involved in a negative feedback loop together. High blood levels of IGF1 lead to decreased secretion of growth hormone, not only by directly supressing the somatotroph, but by also stimulating the release of somatostatin.

Figure 3: Control of Growth Hormone Secretion

Uses

Pharmaceutical and Biotechnological:

Uses involve growth hormone therapy in which GH is used to treat various medical conditions. In the past, GH collected and purified from cadavers was used to treat children with short stature. With modern technology, GH can be collected by recombinant DNA technology.

Another use of GH is for dairy cattle to enhance milk production. As well, it is used in raising pig to reduce fat deposition and enhance muscle growth.

Athletes sometimes use GH to enhance their athletic performance, as well as some people use GH to fight against the appearance of aging.

Disorders

Deficiency: In children, a GH deficiency results in growth failure, short stature and dwarfism. In adults, GH deficiency is rare, and is usually related to a problem in pituitary functioning.

Excess: An excess secretion of GH can result in two disorders.

Gigantism begins in young children or adolescents. It is a rare disorder and is usually caused by GH-secreting tumors located on the pituitary. Robert Wadlow was a famous giant, when he died at the age of 22, he weighed 490lbs. and reached a height of 8ft 11in.

Acromegaly is the second disorder associated with excess GH in adults who have pituitary tumors. Extreme growth of extremities (toes and fingers) along with the jaw are effects of the disorder.



















Figure 4: Robert Wadlow


References:
[1] Cocchi, D., Locatelli, V., Muller, E.E. (Eds.). (1993). Growth Homone and Somatomedins during Lifespan. Germany: Springer-Verlag.
[2] Daughaday, W.H., Harvey, S., Scanes, C.G., (1995). Growth Hormone. Florida, USA: CRC Press.
[3] Muller, E.E., Pecile, A. (1975). Growth Hormone and Related Peptides. Amsterdam: Excerpta Medica
[4] Strand, F.L. (1999). Neuropeptides: Regulators of Physiological Processes. London, England: The MIT Press