Growth hormone, also known as somatotropin, is a protein 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. It is also of considerable interest as a drug used in both humans and animals.
A critical concept in understanding human growth hormone, hgh, activity is that it has two distinct types of effects:
Direct effects are the result of human growth hormone (HGH) binding its receptor on target cells. Fat cells (adipocytes), for example, have human growth hormone receptors, and HGH 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), secreted from
the liver and other tissues in response to HGH. A majority
of the cell promoting effects is actually due to
IGF-1 acting on its target cells.
Keeping this distinction in mind, we can discuss two
major roles of HGH and its minion IGF-1 in physiology.
Effects on Height
This is a very complex process, and requires the coordinated action of several hormones. The major role in gaining height is to stimulate the liver and other tissues to secrete IGF-1. IGF-1 stimulates proliferation of chondrocytes (cartilage cells), resulting in bone development. Human Growth hormone does seem to have a direct effect on bone development in stimulating differentiation of chondrocytes.
IGF-1 also appears to be the key player in muscle development. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.
HGH has important effects on protein, lipid and carbohydrate metabolism. In some cases, a direct effect has been clearly demonstrated, in others, IGF-1 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, human 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: HGH enhances the utilization of fat by stimulating triglyceride breakdown and oxidation in adipocytes.
Carbohydrate metabolism: HGH is one of many that serves to maintain blood glucose within a normal range. It 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, administrationstimulates insulin secretion, leading to hyperinsulinemia.
Control of Secretion
Production of HGH is modulated by many factors, including stress, exercise, nutrition, sleep and HGH itself. However, its primary controllers are two hypothalamic hormones and one from the stomach:
Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that stimulates both synthesis and secretion.
Somatostatin (SS) is a peptide produced by several tissues in the body, including the hypothalamus. Somatostatin inhibits HGH release in response to GHRH and to other stimulatory factors such as low blood glucose concentration.
Ghrelin is a peptide secreted from the stomach. Ghrelin binds to receptors on somatotrophs and potently stimulates secretion.
Human Growth hormone secretion is also part of a negative
feedback loop involving IGF-1. High blood levels of IGF-1 lead to
decreased secretion not only by directly
suppressing the somatotroph, but by stimulating release of
somatostatin from the hypothalamus.
HGH 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 synthesis and secretion lead to a pulsatile pattern of release. Basal concentrations in blood are very low. In children and young adults, the most intense period of HGH release is shortly after the onset of deep sleep.
States of both deficiency and excess provide very visible testaments to the role of it 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, but in the target cell's response.
Clinically, deficiency or receptor defects show up as retardation or dwarfism. The manifestation of HGH 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 is also very dependent on the age of onset and is seen as two distinctive disorders:
Giantism is the result of excessive secretion that begins in young children or adolescents. It is a very rare disorder, usually resulting from a tumor of somatotropes. One of the most famous giants was a man named Robert Wadlow. He weighed 8.5 pounds at birth, but by 5 years of age was 105 pounds and 5 feet 4 inches tall. Robert reached an adult weight of 490 pounds and 8 feet 11 inches in height. He died at age 22.
Acromegaly results from excessive secretion in adults. The onset of this disorder is typically insideous. Clinically, an overdevelopment of bone and connective leads to a change in appearance that might be described as having "coarse features". The excessive human growth hormone and IGF-1 also lead to metabolic derangements, including glucose intolerance.
Pharmaceutical and Biotechnological Uses
In years past, HGH purified from human cadaver pituitaries was used to treat children with severe height retardation. More recently, the virtually unlimited supply of recombinant HGH has lead to several other applications to human and animal populations.
It is commonly used to treat children of pathologically short stature. There is concern that this practice will be extended to treatment of essentially normal children - so called "enhancement therapy" on demand. Similarly, HGH has been used by some to enhance atheletic performance. Although HGH therapy is generally safe, it is not as safe as no therapy and does entail unpredictable health risks. Parents that request HGH therapy for
The role of human growth hormone in normal aging remains poorly understood, but some of the cosmetic symptoms of aging appear to be amenable to this therapy. This is an active area of research, and additional information and recommendations about risks and benefits will undoubtedly surface in the near future.
Human growth hormone facts therapy is currently approved and marketed for enhancing milk production in dairy cattle. There is no doubt that administration of bovine somatotropin to lactating cows results in increased milk yield, and, depending on the way the cows are managed, can be an economically-viable therapy. However, this treatment engenders abundant controversy, even among dairy farmers. One thing that appears clear is that drinking milk from cattle treated with bovine growth hormone facts does not pose a risk to human health.