Deficiency of growth hormone and IGF-1 reduces cancer and kidney disease, but creates other problems

03/22/05

WINSTON-SALEM, N.C. Deficiencies of growth hormone and similar compounds may reduce cancer and kidney disease late in life, but also may lead to cartilage degeneration and impaired memory and learning ability, according to research at Wake Forest University Baptist Medical Center and four other institutions.

The researchers used a rat model to explore the effects of growth hormone and another compound, IGF-1 (insulin-like growth factor 1) on adult rats and found paradoxical effects, according to William E. Sonntag, Ph.D., professor of physiology and pharmacology at Wake Forest University Baptist Medical Center and the lead investigator.

"Things that happen when you are an adolescent may have an impact on how long you live and what you die of," he said.

"The presence of growth hormone and IGF-1 is necessary for maintenance of cognitive function and prevention of cartilage degeneration," Sonntag and his colleagues reported in an article in Endocrinology, published on-line today. But the hormones also increase cancer and other diseases that limit lifespan.

The researchers developed a strain of dwarf rats that were naturally deficient in both growth hormone and in IGF-1. To mimic the rise in growth hormone and IGF-1 during adolescence in normal rats, some of these deficient rats were given growth hormone while they were between 4 and 14 weeks of age rat adolescence. Then hormone treatment was stopped and the animals had lower growth hormone and IGF-1 levels the rest of their lives.

That had an effect on cancer: 88 percent of "normal" male rats have tumors at death. The male rats that had a lifelong deficiency of growth hormone had substantially fewer tumors 63 percent and the percent of tumors that were fatal was reduced from 57 percent to 31 percent.

The same pattern occurred for kidney disease, which was found in 74 percent of the normal male animals at the time of their deaths. None of the growth-hormone deficient animals developed kidney disease.

They found that animals with a deficiency in growth hormone initiated after adolescence had up to a 14.6 percent increase in lifespan. All animals in the study lived until they died of natural causes.

The researchers used several tests to measure memory and learning. They found that growth-hormone-deficient rats had impaired learning ability compared to normal animals of the same age. A similar pattern occurred in memory tests.

"The presence of growth hormone and IGF-1 are required for optimal performance on tests of learning and memory throughout life," they said. "Growth hormone/IGF-1 replacement in older animals reverses the age-related decline in cognitive function."

The group also found that "cartilage degeneration that normally accompanies aging is accelerated by the absence of growth hormone."

The researchers concluded that cancer risk as well as other age-related pathologies could be substantially decreased in these animals by inducing a modest deficiency of growth hormone and IGF-1 early in life. However, there is a tradeoff and deficiency of growth hormone and IGF-1 may impair learning and memory and accelerate some degenerative diseases.

Source: Eurekalert & others

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