Impact of exogenous growth hormone on host preservation and tumor cell-cycle distribution in a rat sarcoma model.
Growth hormone (hGH) has been reported to improve nitrogen balances and accrue lean mass tissue in stable subjects. However, the ability of hGH to positively influence host preservation in stressed catabolic states such as cancer-induced cachexia remains unproven. Thirty-seven sham or tumor implanted Fischer 344 rats were randomized to receive either 0.5 mg/kg/day hGH or saline (SAL) subcutaneously from Days 14 to 23 postimplantation. Plasma levels of hGh and somatomedin C/insulin-like growth factor I (IGF I) as well as IGF I bioactivity were determined at sacrifice. Gastrocnemius muscle protein content was used as a index of host lean tissue mass and the tumor response was evaluated via flow cytometry for analysis of cell-cycle distribution. Host cachexia was not attenuated by hGH as muscle protein content was similar in hGH and saline-treated groups. Despite elevated hGH levels (range, 77-222 ng/ml (GH) vs less than 2 ng/ml (SAL], IGF I levels and bioactivity were not elevated in GH-treated groups. In contrast, cancer-induced anorexia markedly decreased IGF I levels (4 U/ml vs 9 U/ml, NTB; P less than 0.01) and this response remained refractory to hGH administration. While final tumor weights were similar between GH- and SAL-treated groups, hGH treatment caused a twofold increase in the proportion of aneuploid cells (P less than 0.05). In conclusion, hGH failed to attenuate lean mass dissolution in the tumor bearing host and this response may be related to the failure of IGF I induction. Conversely, the altered proportion of tumor aneuploid cells suggests a direct influence on tumor cell-cycling populations.
Ng
E H
EH
Department of Surgery, New York Hospital-Cornell Medical Center, New York 10021.
Rock
C S
CS
Lazarus
D
D
Staiano-Coico
L
L
Fischer
E
E
Moldawer
L L
LL
Lowry
S F
SF
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology*; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D012016:Reference Values; D012513:Sarcoma, Experimental / Q000473:pathology*
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone