Effect of growth hormone and protein intake on tumor growth and host cachexia.
BACKGROUND
Growth hormone supplementation has been shown to stimulate muscle protein synthesis and to improve nitrogen balance in a variety of catabolic states. The role of growth hormone to support the tumor-bearing host is complicated by the risk that growth hormone or its intermediaries may stimulate tumor growth. The purpose of this study is to examine the effect of growth hormone supplementation in tumor-bearing rats. This is studied in the protein-fed and protein-starved state in an attempt to isolate a selective benefit for the host over the tumor.


METHODS
Forty Lewis rats bearing a metastatic mammary adenocarcinoma (MAC-33) were divided into four groups: one receiving a regular diet plus saline solution, one receiving a regular diet plus growth hormone (1 IU/kg/day), one receiving protein-depleted diet plus saline solution, and one receiving a protein-depleted diet plus growth hormone. After 25 days of growth hormone treatment, animals were killed to determine primary tumor size, tumor/carcass ratio, host organ composition, pulmonary metastasis, and serum amino acid levels.


RESULTS
The tumor/carcass ratio was decreased as a result of growth hormone treatment in both the protein-fed and protein-starved groups. Growth hormone supplementation resulted in increased carcass weight, muscle weight, and muscle protein content in the protein-fed, tumor-bearing animals (p < 0.05). In the protein-starved, tumor-bearing rats growth hormone supplementation resulted in a significant decrease in tumor volume and tumor protein content. Amino acid analysis suggests that the amino acid tyrosine is a rate-limiting substrate for tumor cell proliferation in this model.


CONCLUSIONS
Growth hormone has a differential effect on tumor and host growth in the protein-fed and protein-starved state. Growth hormone supplementation inhibited tumor growth in protein-deprived animals. This is most likely accomplished indirectly by limiting amino acid substrate availability to the tumor.
Bartlett
D L
DL
Hospital of the University of Pennsylvania, Philadelphia 19104.
Stein
T P
TP
Torosian
M H
MH
D000230:Adenocarcinoma / Q000150:complications / Q000378:metabolism / Q000473:pathology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002100:Cachexia / Q000209:etiology / Q000517:prevention & control*; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D009124:Muscle Proteins / Q000096:biosynthesis; D009929:Organ Size; D051381:Rats; D011917:Rats, Inbred Lew
D000596:Amino Acids; D004044:Dietary Proteins; D009124:Muscle Proteins; D013006:Growth Hormone