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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.
Physiologic Effects
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.
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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.
Metabolic Effects
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.
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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.
Disease States
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.
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Human Growth Hormone Information and Explanations
Research Articles
Back to Basics
HGH
Explanation
Aging
Somatostatin
Ghrelin the Peptide Hormone
Endocrinologists Disorders
First Recombinant DNA
Growth Hormone
Deficiency
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