Strong Muscles, Strong Tumors? Growth hormone's effects on cancer cells raise concerns about therapy
Authors: Davenport R. John 
Published: August 2003

Unique supplement! Guaranteed results! Erases wrinkles! Ads for growth hormone (GH) replacement therapy promise to ameliorate the effects caused by decreases in circulating hormone levels as people age. Although GH therapy appears beneficial by some measures--it seems to tone muscles, for example--possible negative impacts of long-term treatment are unknown. New results suggest that blocking a GH-containing hormone network slows the duplication of tumor cells. The work adds to growing evidence that GH as well as insulin-like growth factor-1 (IGF-1) stimulates cancer growth, and it supports the notion that people should approach GH therapy with caution.
In their efforts to design cancer-fighting drugs, Szepeshazi and colleagues investigated whether compounds that inhibit growth hormone releasing hormone (GHRH) affect breast cancer growth in mice. GHRH stimulates the release of GH from the pituitary gland; circulating GH in turn triggers production of other hormones, including IGF-1, which is known to stimulate the growth of tumor cells. Recent work indicates that tumor cells as well as the pituitary gland can manufacture GH, and some data suggest that GH stimulates cancer cell growth. In addition, GHRH antagonists can slow the duplication of some cancer cells without altering the amounts of GH and IGF-1 in the bloodstream. That observation has led researchers to propose that local action, in addition to systemic effects, of hormones might be critical for cancer growth, but no one yet understands the relevant mechanisms.

In the new work, the researchers found that GH dramatically spurs reproduction of cultured breast cancer cells as compared with untreated controls or IGF-1-exposed cells and that GHRH antagonists block this stimulation. The researchers also transplanted mammary tumors into mice and treated the animals with one of two GHRH antagonists. After 18 days, tumors in control mice dwarfed those in animals treated with the antagonists. In addition, drug-exposed mice carried smaller amounts of GH and IGF-1 proteins and messenger RNAs (mRNAs) in their tumors than did controls. With treatment, mRNA levels of the cell surface receptor required for GH-induced stimulation decreased in the tumor cells as well. The results support the idea that tumors manufacture GH locally and that this hormone might accelerate cancer growth. GH's healthful effects had already come under suspicion: Extra GH might increase muscle vitality in old age, but disruption of the GH/IGF-1 pathway in model organisms can lead to unusual longevity (see
"Growing Old Together"
). No studies have probed whether long-term treatment with GH results in an increased cancer risk in humans, and growing evidence suggests that hormone treatment in the elderly requires deliberate study.

--R. John Davenport; suggested by James M. Harper

K. Szepeshazi, A. V. Schally, P. Armatis, K. Groot, F. Hebert, A. Feil, J. L. Varga, G. Halmos, Antagonists of GHRH decrease production of GH and IGF-I in MXT mouse mammary cancers and inhibit tumor growth.
Endocrinology
142
, 4371-4378 (2001).
[Abstract]
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