Growth Hormone and the National Institute of Health

Hormones. In 1989, at Veterans Administration hospitals in Milwaukee and Chicago, a small group of men aged 60 and over began receiving injections three times a week that dramatically reversed some signs of aging. The injections increased their lean body (and presumably muscle) mass, reduced excess fat, and thickened skin. When the injections stopped, the men's new strength ebbed and signs of aging returned.

What the men were taking was recombinant human growth hormone (GH), a synthetic version of the hormone that is produced in the pituitary gland and plays a critical part in normal childhood growth and development. Now researchers are learning that GH, or the decline of GH, seems also to play a role in the aging process in at least some individuals.

The idea that hormones are linked to aging is not new. We have long known that some hormones decline with age. Human growth hormone levels decrease in about half of all adults with the passage of time. Production of the sex hormones estrogen and testosterone tends to fall off. Hormones with less familiar names, like melatonin and thymosin, are also not as abundant in older as in younger adults.

Growth Hormone. This product of the pituitary gland appears to play a role in body composition and muscle and bone strength. It is released through the action of another trophic factor called growth hormone releasing hormone, which is produced in the brain. It works by stimulating the production of insulin-like growth factor, which comes mainly from the liver. All three are being studied for their potential to strengthen muscle and bones and prevent frailty among older people.

Growth Factors. Hormones are aided and abetted by an arsenal of other substances that also stimulate or modulate cell activities. Known collectively as growth or trophic factors, these include substances such as insulin-like growth factor (IGF-1), which mediates many of the actions of GH. Another trophic factor of interest to gerontologists is growth hormone releasing hormone, which stimulates the release of GH.

The mechanisms -- how hormones and growth factors produce their effects -- are still a matter of intense speculation and study. Scientists know that these chemical messengers selectively stimulate cell activities which in turn affect critical events, such as the size and functioning of skeletal muscle. However, the pathway from hormone to muscle is complex and still unclear.

Consider growth hormone. It begins to stimulating production of insulin-like growth factor. Produced primarily in the liver, IGF-1 enters and flows through the blood stream, seeking out special IGF-1 receptors on the surface of various cells, including muscle cells. Through these receptors it signals the muscle cells to increase in size and number, perhaps by stimulating their genes to produce more of special, muscle-specific proteins. Also involved at some point in this process are one or more of the six known proteins that bind with IGF-1; their regulatory roles are still a mystery.

As if the cellular complexities weren't enough, the action of growth hormone also may be intertwined with a cluster of other factors -- exercise, for example, which stimulates a certain amount of GH secretion on its own, and obesity, which depresses production of GH. Even the way fat is distributed in the body may make a difference; lower levels of GH have been linked to excess abdominal fat but not to lower body fat.