GROWTH HORMONE(Somatotropin)

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 supresses their ability to take up and accumulate circulating lipids.

Indirect effects; are mediated primarily by a insulin-like growth factor-I (IGF-I)( somatomedin C) 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 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 OF GROWTH HORMONE

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.

APPLIED PHYSIOLOGY

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 insideous, 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 hyperglycemi