Growth hormone, also known as somatotropin

·        a protein hormone of about 190 amino acids that is synthesized and secreted by cells called somatotrophs in the anterior pituitary.

·        It is a major participant in control of several complex physiologic processes, including growth and metabolism.

·        Growth hormone is also of considerable interest as a drug used in both humans and animals.

Physiologic Effects of Growth Hormone

• Direct effects: are the result of growth hormone binding its receptor on target cells. Fat cells (adipocytes), for example, have growth hormone receptors, and growth hormone stimulates them to break down triglyceride and supresses their ability to take up and accumulate circulating lipids.
• Indirect effects: are mediated primarily by a insulin-like growth factor-1 (IGF-1), a hormone that is secreted from the liver and other tissues in response to growth hormone. A majority of the growth promoting effects of growth hormone is actually due to IGF-1 acting on its target cells.

Effects on Growth

·        The major role of growth hormone in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1.

o       IGF-1 stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth.

o       Growth hormone does seem to have a direct effect on bone growth in stimulating differentiation of chondrocytes.

o       IGF-1 also appears to be the key player in muscle growth.

§         It stimulates both the differentiation and proliferation of myoblasts.

§         It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.

Metabolic Effects

·        Growth hormone has important effects on protein, lipid and carbohydrate metabolism.

·         Protein metabolism: growth hormone stimulates protein anabolism in many tissues. This effect reflects increased amino acid uptake, increased protein synthesis and decreased oxidation of proteins.

·         Fat metabolism: Growth hormone enhances the utilization of fat by stimulating triglyceride breakdown and oxidation in adipocytes.

·         Carbohydrate metabolism: Growth hormone is one of many hormones serving to maintain blood glucose within a normal range. Growth hormone is often said to have anti-insulin activity, because it supresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues and enhance glucose synthesis in the liver. Somewhat paradoxically, administration of growth hormone stimulates insulin secretion, leading to hyperinsulinemia.

Control of Growth Hormone Secretion

Production of growth hormone is modulated by many factors, including stress, exercise, nutrition, sleep and growth hormone itself. However, its primary controllers are two hypothalamic hormones and one hormone from the stomach:

• Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that stimulates both the synthesis and secretion of growth hormone.
• Somatostatin (SS) is a peptide produced by several tissues in the body, including the hypothalamus. Somatostatin inhibits growth hormone release in response to GHRH and to other stimulatory factors such as low blood glucose concentration.
• Ghrelin is a peptide hormone secreted from the stomach. Ghrelin binds to receptors on somatotrophs and potently stimulates secretion of growth hormone.

Growth hormone secretion is also part of a negative feedback loop involving IGF-1.

·        High blood levels of IGF-1 lead to decreased secretion of growth hormone not only by directly suppressing the somatotroph, but by stimulating release of somatostatin from the hypothalamus.

·        Growth hormone also feeds back to inhibit GHRH secretion and probably has a direct (autocrine) inhibitory effect on secretion from the somatotroph.

·        Integration of all the factors that affect growth hormone synthesis and secretion lead to a pulsatile pattern of release.  Basal concentrations of growth hormone in blood are very low. In children and young adults, the most intense period of growth hormone release is shortly after the onset of deep sleep.

Disease States

States of both growth hormone deficiency and excess provide very visible testaments to the role of this hormone in normal physiology. Such disorders can reflect lesions in either the hypothalamus, the pituitary or in target cells. A deficiency state can result not only from a deficiency in production of the hormone, but in the target cell's response to the hormone.

Clinically, deficiency in growth hormone or receptor defects are as growth retardation or dwarfism. The manifestation of growth hormone deficiency depends upon the age of onset of the disorder and can result from either heritable or acquired disease.

The effect of excessive secretion of growth hormone is also very dependent on the age of onset and is seen as two distinctive disorders:

• Giantism –during youth
• Acromegaly – during adulthood