SCIENCE INDEX 2000 2001 2002 Biology

Growth hormone may boost production of disease-fighting cells in elderly

Jim Barlow, Life Sciences Editor
(217) 333-5802; b-james3@uiuc.edu

2/6/02

CHAMPAIGN, Ill. – Growth-hormone therapy in elderly patients increases lean body mass and reduces body fat, helping them maintain fitness. Now, scientists say, the therapy also may dramatically boost the production of cells vital to fighting disease.

The conclusion is based on a study published in the February issue of the journal Endocrinology. Using aging rats, researchers at the University of Illinois found that injected or implanted growth hormone stimulated the production of immunity-promoting hematopoietic cells in bone marrow, as well as in the spleen, liver and adrenal glands. Production in the treated elderly (2-year-old) rats was three times that of similarly aged, untreated rats and 80 percent of that in the more fit younger rats in the control group.

"By 60 years of age, 30 percent of men have dramatically low concentrations of plasma insulin-like growth hormone-1 (IGF-I), falling to levels found in growth-hormone deficient children," said Keith W. Kelley, lead investigator and professor of animal sciences in the UI Laboratory of Immunophysiology. "This is known as the somatopause of aging."

Some physicians now prescribe growth-hormone therapy to the elderly in an effort to counteract the effects of somatopause.

"These new results show that growth hormone therapy of aged animals totally reverses the accumulation of fat cells in the bone marrow," Kelley said. "This reduction in fat cells is accompanied by a huge increase in the number of both red and white blood cells in the bone marrow, which is dramatically reduced in the elderly. These results establish that a classic hormone, GH, is a potent stimulator of the production of blood cells."

Such a production process is called hematopoiesis. "If similar results occur in the aged human, this kind of treatment approach could lead to an increase in the reserve capacity of both red and white cells," Kelley said.

Normal growth hormone production declines as people age. Muscle size and tone wane, and fat accumulates not only in readily visible areas of the body but also within bone marrow, where it fills a void created by a declining number of hematopoietic cells.

The researchers wrote that they "favor the view that IGF-I is the critical molecule that acts directly on progenitor cells to promote hematopoiesis." IGF-I, a protein, is a growth factor that is released from the liver and local tissues after stimulation by growth hormone. It is considered a key regulator of body growth, including muscle synthesis.

Kelley's team implanted either synthetic growth hormone-secreting pituitary epithelial cells or injected recombinant growth hormone into their experimental rats. Both approaches yielded positive changes.

Previous research, based on a "simplistic approach of preparing single-cell suspensions from whole tissue and counting the resulting cells" after adding growth hormone, the authors wrote, had led to the belief that growth hormone only partially reversed age-associated declines in the production of hematopoietic tissue.

Kelley's team used histological techniques, which allowed researchers to clearly see the effects of their delivery of growth hormone on the hematopoietic tissue. What they discovered, they wrote, "is the most complete morphological restoration" of the production of these cells that has ever been reported.

The researchers who conducted the study were Sean Arkins, Suzanne Broussard, Richard A. French, Christian Minshall (a UI medical student now completing his residency in pathology), and Kelley, all of the UI Laboratory of Immunophysiology in the department of animal sciences; William A. Meier and James F. Zachary, both of the department of veterinary pathobiology in the UI College of Veterinary Medicine; and Robert Dantzer of the National Institute for Agricultural Research in France. Arkins and French were doctoral students and now are at the University of Limerick in Ireland and the University of Connecticut in Storrs, respectively.

The National Institutes of Health and the Pioneering Research Project in Biotechnology, a program of the Japanese Ministry of Agriculture, Forestry and Fisheries, funded the research.