Growth Hormone (Somatotropin)
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Growth hormone is 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
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
(adipocytes), for example, have growth hormone
receptors, and growth hormone stimulates them to
break down triglyceride and suppresses 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.
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 suppresses 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.
Clinically, deficiency in growth hormone or defects in its binding to receptor are seen 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 is the result of excessive growth hormone 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 of growth hormone in adults, usually
the result of benign pituitary tumors. The onset of this disorder is typically insidious,
occurring over several years. Clinical signs of acromegaly include overgrowth of
extremities, soft-tissue swelling, abnormalities in jaw structure and cardiac disease. The
excessive growth hormone and IGF-I also lead to a number of metabolic derangements,
including hyperglycemia.
Pharmaceutical and Biotechnological Uses of Growth Hormone
In years past, growth hormone purified from human cadaver pituitaries was used to
treat children with severe growth retardation. More recently, the virtually unlimited
supply of growth hormone produced using recombinant DNA technology has lead to
several other applications to human and animal populations.
Human growth hormone 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" or growth hormone on demand.
Similarly, growth hormone has been used by some to enhance athletic performance.
Although growth hormone therapy is generally safe, it is not as safe as no therapy and
does entail unpredictable health risks. Parents that request growth hormone therapy
for children of essentially-normal stature are clearly misguided.
The role of growth hormone in normal aging remains poorly understood, but some of
the cosmetic symptoms of aging appear to be amenable to growth hormone therapy.
This is an active area of research, and additional information and recommendations
about risks and benefits will undoubtedly surface in the near future.
Growth hormone 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 does not pose a risk to human
health.
Another application of growth hormone in animal agriculture is treatment of growing
pigs with porcine growth hormone. Such treatment has been demonstrated to
significantly stimulate muscle growth and reduce deposition of fat.
Posted here with permission
Richard Bowen, January 16, 2008
Colorado State
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Aging process
Arginine inhibits one of the
mechanisms of the aging
process (it inhibitx the
process of cross-linking).
Radner, W., et al., NMRI-mouse. J
Gerontol. 49(2):M44-M46. 1994.
Health benefits of Arginine by Dr.
Harry Elwardt
Arginine increases the
release of the Human
Growth Hormone (HGH)
(Also known as the
anti-aging hormone) from
the pituitary gland. Gianotti L,
Macario M, Lanfranco F, et al J Clin
Endcrinol Metab 2000
Oct;85(10):3604-8.
Arginine inhibits one of the
mechanisms of the aging
process (it inhibitx the
process of cross-linking).
Radner, W., et al., NMRI-mouse. J
Gerontol. 49(2):M44-M46. 1994.
Health benefits of Arginine by Dr.
Harry Elwardt
Arginine increases the
release of the Human
Growth Hormone (HGH)
(Also known as the
anti-aging hormone) from
the pituitary gland. Gianotti L,
Macario M, Lanfranco F, et al J Clin
Endcrinol Metab 2000
Oct;85(10):3604-8.
CONTACT US AT:
The Stewardship Group
info@stewardshipgroup.
net
918-747-7292
The Stewardship Group
info@stewardshipgroup.
net
918-747-7292
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