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September 22, 1998

Response to synthetic growth hormone depends on dosage

SAN FRANCISCO — Researchers at the University of Washington in Seattle have shown that older women’s response to treatment with GHRH (a synthetic form of growth hormone releasing hormone) is directly related to the dosage.

Dr. Robert Schwartz, UW professor of medicine in the Division of Geriatrics and Gerontology, presents findings of his research team at the International Growth Hormone Research Society Meeting in San Francisco, Sept. 3-6.

Schwartz explains that the aging pituitary gland’s decreasing production of growth hormone seems to account for many complaints of older age: loss of muscle mass, strength and endurance, and increase in body fat.

Researchers first noted the effects of loss of growth hormone when they studied young people deficient in natural growth hormone, from such causes as a pituitary tumor. They were given injections of growth hormone to help them grow. Once they achieved the desired height, growth hormone was withdrawn, because it was expensive and rare. Without the growth hormone, the result was young people who developed conditions usually found in the elderly: heart disease, high blood pressure, depression, and reduced strength and endurance.

Schwartz and his colleagues have been studying growth hormone for a number of years. In the study reported in San Francisco, they address a number of questions revolving around what is called the growth hormone axis.

“The body has more than one site and more than one process for maintaining an appropriate level of growth hormone,” explains Schwartz. “It includes the hypothalmus, the pituitary gland, and peripheral tissues. A whole cascade of events feed back on each other. The hypothalmus produces growth hormone releasing hormone (GHRH), which stimulates the pituitary to produce growth hormone (GH), which stimulates tissues throughout the body to produce insulin-like growth factor one (IGF-I). As people get older, their growth hormone secretion declines tremendously, along with their levels of IGF-I.”

Previous studies had shown that older people are resistant to the effects of GHRH. They were given an injection, but their GH didn’t go up and their IGF-I didn’t go up very much either. “It wasn’t clear if the pituitary couldn’t make GH or if it was just ‘sleeping’,” says Schwartz.

In the current study, the UW researchers found that the pituitary was, indeed, just sleeping. “We gave GHRH and found that we could wake up the pituitary. It would secrete GH, which in turn produced IGF-I. If you give small doses of GHRH, you get a small response of GH, which we determined by measuring levels of IGF-I. The pituitary gland in older people responds in a dose-reponsive manner.”

The researchers tested effects of single nightly doses of GHRH in 12 healthy women over 60. GHRH or a placebo was given for successive one-month periods, at increasing doses. They found there was a dose-related increase in IGF-I levels, and improvements in lean body mass, motor performance, muscle strength, and quality of life as measured by questionnaire.

What the research shows, says Schwartz, is that the problem in older individuals is their ability to modulate the growth hormone axis above the level of the pituitary: at the level of GHRH or above. “We can give GHRH and the pituitary will secrete GH.”

The advantage of giving synthetic GHRH instead of synthetic GH, he explains, is that one can bypass the counter-regulatory mechanisms: If you receive too much GH, for example, the body will shut the whole system down. But by giving GHRH, the system should be responsive, and there may be fewer adverse effects.

The hope of this and future research, says Schwartz, who has now spent six years studying supplementation with GHRH, is that we may be able to reverse some of the problems of aging, through supplementation with GHRH. “Studies have shown that the loss of muscle mass, endurance and strength and fat gain occurs at the same time there is a tremendous decline in growth hormone,” he says. “The question is, are some of these declines related to this deficit? Would supplementation make people feel better?”

With increasing confidence, researchers can answer yes to these questions, while calling for studies of larger size and longer duration.

The GHRH research was funded by Serono Laboratories, which provided the GHRH used in the study.