Growth Hormone (Somatotropin)

Growth hormone is a naturally released anabolic hormone by the pituitary gland. It promotes muscle growth and the breakdown of body fat for energy. Unfortunately it is greatly reduced after the age of about 20

Physiologic Effects of Growth Hormone

A critical concept in understanding growth hormone activity is that it has two distinct types of effects:

• Direct effects are the result of growth hormone binding its receptor on target cells. Fat cells have growth hormone receptors. Growth hormone stimulates fat cells 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-I (IGF-I), 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-I acting on its target cells.
Keeping this distinction in mind, we can discuss two major roles of growth hormone and its minion IGF-I in physiology.

Effects on Growth

Growth is a very complex process, and requires the coordinated action of several hormones. The major role of growth hormone in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-I. IGF-I stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth. Growth hormone does seem to have a direct effect on bone growth in stimulating differentiation of chondrocytes.IGF-I 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. In some cases, a direct effect of growth hormone has been clearly demonstrated, in others, IGF-I is thought to be the critical mediator, and some cases it appears that both direct and indirect effects are at play.
• Protein metabolism: In general, 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 a battery of hormones that serves 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-I. High blood levels of IGF-I 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.

Adult Growth hormone deficiency

Growth hormone deficiency in adults has been associated with a mixture of symptoms that are similar to those described by fibromyalgia patients: low energy , poor general health , reduced exercise capacity , muscle weakness , cold intolerance, impaired cognition, dysthymia and decreased lean body mass Consequences of adult GH Deficiency GH is important in maintaining muscle homeostasis, and it was theorized that sub-optimal levels might be a factor in the impaired resolution of muscle microtrauma. The treatment of GH deficiency in adults has been reported to improve quality of life and energy level, reduce pain, improve depression, enhance self esteem, improve cholesterol and LDL levels , enhance cognitive psychometric performance, augment stroke volume, and improve exercise capacity and muscle strength .