The Growth Hormone: Insulin-like Growth Factor 1 Axis Is a Mediator of Diet Restriction-induced Inhibition of Mononuclear Cell Leukemia in Fischer Rats

摘要: Abstract A leukemia cell transplant model and both in situ vitro bioassays were used to assess the roles of endogenous factors mediating diet restriction (DR)-induced inhibition mononuclear (MNCL) Fischer 344 rats. DR-treated male rats ( n = 35), which fed 75% ad libitum (AL) intake NIH-07 open formula diet, had lower transplanted MNCL incidence (54 versus 77%; P 0.039) with longer latency 0.015) decreased severity 0.01) than AL-treated 12 weeks after inoculation cells. Five-day proliferation rates cultured (CRNK-16) cells diffusion chambers implanted 22% less 0.03), indicating that DR-dependent diffusible factor(s) modulate growth. Serum from supported CRNK-16 relative serum levels growth hormone (GH) insulin-like factor 1 (IGF-1) over 50% DR- An evaluation proliferative activity a panel purified showed GH IGF-1, but not 15 other factors, stimulated thymidine incorporation Infusion either or IGF-1 via osmotic minipumps restored up measured Splenocytes rats, more sensitive mitogen stimulation, displayed increased surface expression receptors for class 2 major histocompatibility complex molecules, cytotoxic target tumor further enhanced responsiveness natural cytotoxicity reversed DR-induced increase receptors. We conclude DR modulates progression through its influence on suppression GH:IGF-1 axis enhancement host defenses against