Human growth hormone (HGH)

The pituitary releases several hormones including growth hormone, prolactin and placental lactogen. GH is secreted into the blood by the somatotrope cells of the anterior pituitary gland, in larger amounts than any other pituitary hormone. The transcription factor PIT-1 stimulates both the development of these cells and their production of GH. Failure of development of these cells, as well as destruction of the anterior pituitary gland, results in GH deficiency. The release of GH from somatotroph cells of the anterior pituitary gland is a complex process involving multiple regulators. The hypothalamic peptide GHRH (growth hormone-releasing hormone) acts on the somatotrophs to release GH, while the inhibitory peptide somatostatin blocks GH release. The body binds most of the growth hormone in the liver and converts some into Somatomedin-C, another protein hormone also called Insulin-like Growth Factor- I (IGF-I). Growth hormone releasing hormone (GHRH) from the arcuate nucleus and ghrelin promote GH secretion, and somatostatin from the periventricular nucleus inhibits it.

Functions and health benefits of growth hormone

Human growth hormone is essential to growth. It is a supplement given to children who suffer with abnormally slow bone growth to enable them to grow taller. GH directly stimulates division and multiplication of chondrocytes of cartilage. These are the primary cells in the growing ends (epiphyses) of children's long bones (arms, legs, digits). GH also stimulates production of insulin-like growth factor 1 (IGF1, also known as somatomedin C), a hormone homologous to proinsulin. IGF-1 helps the cartilage cells located at the ends of long bones to multiply. In children, this leads to growth in the length of the bones and increases the child's height. The liver is a major target organ of GH for this process, and is the principal site of IGF1 production. IGF1 has growth-stimulating effects on a wide variety of tissues. Additionally, some IGF1 is generated within target tissues, making it apparently both an endocrine and an autocrine hormone. Man-made growth hormone may be used in children who have certain conditions that cause failure to grow normally. These conditions include growth hormone deficiency (inability to produce enough growth hormone), kidney disease, and Turner's syndrome.

GH stimulates the immune system. Growth hormone is used in adults to treat growth failure and to treat weight loss caused by acquired immunodeficiency syndrome (AIDS). AIDS wasting syndrome involves severe weight loss, but what's most devastating is the loss of muscle or lean body mass. This condition can often be improved with appetite stimulants and exercise. hGH causes growth and repair of body tissues including the muscles, the skin, and the kidneys. HGH injections can also help them gain body mass.

GH plays a role in fuel homeostasis. GH reduces liver uptake of glucose, an effect that opposes that of insulin. GH also contributes to the maintenance and function of pancreatic islets. It tends to promote lipolysis, which results in some reduction of adipose tissue (body fat) and rising amounts of free fatty acids and glycerol in the blood. The reduction in GH levels with aging is believed to contribute to age-related decreases in muscle mass and strength and decreased lipolysis. During fetal brain development, GH works closely to stimulate IGF-2 production--known to be one of the primary hormones responsible for cognitive development and IQ in children. IGF-2 is the growth factor that stimulates brain cell growth and development.

Growth hormone deficiency

Deficiency of GH produces significantly different problems at various ages. Deficiency of growth hormone secretion before puberty results in pituitary dwarfism. Growth retardation may become evident in infancy and persist throughout childhood. The child's "growth curve," which is usually plotted on a standardized growth chart by the pediatrician, may range from flat (no growth) to very shallow (minimal growth). Normal puberty may or may not occur, depending on the degree to which the pituitary can produce adequate hormone levels other than growth hormone. In adults the effects of deficiency are more subtle, and may include deficiencies of strength, energy, bone mass, and increased cardiovascular risk. Growth hormone deficiency involves abnormally short stature with normal body proportions. Growth hormone deficiency can be categorized as either congenital (present at birth) or acquired. An abnormally short height in childhood may occur if the pituitary gland does not produce enough growth hormone. It can be caused by a variety of genetic mutations (such as Pit-1 gene, Prop-1 gene, growth hormone receptor gene, growth hormone gene), absence of the pituitary gland, or severe brain injury, but in most cases no underlying cause of the deficiency is found. Acquired GH deficiency is characterized by weight gain, increased fat mass and decreased lean body mass. In one recent study, total body fat was shown to be increased by 7% in this population while lean body mass was decreased to a similar degree.

Growth hormone excess

An excess of growth hormone can lead to gigantism or acromegaly, both of which are characterized by a very large stature. Gigantism is the result of hGH overproduction in early childhood leading to a skeletal height up to 8 feet or more. Excess growth hormone produced after puberty has little effect on the growth of the skeleton, but it results in a disease affecting terminal skeletal structures known as acromegaly. Acromegaly results when hGH is overproduced after the onset of puberty. In this condition, the epiphyseal plates of the long bone of the body do not close, and they remain responsive to additional stimulated growth by hGH. This disorder is characterized by an enlarged skull, hands and feet, nose, neck, and tongue. The primary effect of growth hormone excess in childhood is excessive growth, but the tallness is accompanied by a characteristic body build recognizable to an endocrinologist. The typical body build involves heavy, thick bones, with large hands and feet and a heavy jaw. Once puberty is complete and adult height is achieved, continued thickening of the skin and growth of the jaw results in a combination of features referred to as acromegaly.

Growth hormone treatment

Treatment usually lasts several years, although results are often seen as soon as three to four months after the injections are started. The earlier the treatment for growth hormone deficiency is started, the better chance the child will have of attaining normal or near-normal adult height. In August 1996, the FDA approved HGH for use in adult patients. Before this, it was authorized only for use to promote growth in HGH-deficient children. GH treatment can provide a number of measurable benefits to severely GH-deficient adults, such as enhanced energy and strength, and improved bone density. Muscle mass may increase at the expense of adipose tissue. As of 2004, GH has been approved by the U.S. Food and Drug Administration for treatment of Turner syndrome, chronic renal failure, Prader-Willi syndrome, and idiopathic short stature.

Risks and side effects of HGH treatment

Risks of treatment are quite rare when GH is given in replacement doses to deficient children and adults. Side effects of HGH are not at all the same as with anabolic and androgenic steroids. Most common side effects are hypoglycemia (low blood sugar level) and inadequate thyroid function. Large, pharmacological doses of HGH are often associated with the clinical signs of HGH excess, including fluid retention, carpal tunnel, and hypertension. Supplemental human growth hormone is contraindicated in those with any evidence of active malignancy. It is also contraindicated in those who are hypersensitive to any component of an HGH-containing product.