EFFECTS OF GROWTH-HORMONE SECRETAGOGUES ON AGE-RELATED-CHANGES IN THERAT IMMUNE-SYSTEM

The purpose of this study was to determine whether growth hormone (GH) secretagogues alter age-related changes in the immune system. Fischer 344 female rats, ranging in age from 3 to 28 months at the start of t he study were co-administered GH releasing hormone (GHRH; 3 mu g/kg) a nd GH releasing peptide (GHRP; 100 mu g/kg) to produce episodes of end ogenous GH secretion once daily for 120 consecutive days. Thymus gland weights in the older rats administered saline were significantly less than in younger rats, whereas thymus weights in older rats administer ed the GH secretagogues were the same as in younger rats. Spleen weigh ts were not affected by age or treatment. Fluorescence activated cell sorting (FACS) quantitation of lymphocytes with CD4 and CD8 surface an tigens revealed that in the thymus gland, CD4(+)CD8(+) lymphocytes dec reased while CD4(+)CD8(-), CD4(-)CD8(+), and CD4(-)CD8(-) lymphocytes increased with aging. GHRH and GHRP administration reduced the decreas e in double-labeled thymocytes that occurs during aging. In the spleen , CD4(+)CD8(+) and CD--CD8(+) lymphocytes increased while CD4(-)CD8(-) lymphocytes decreased and CD4(+)CD8(-) lymphocytes remained constant during aging. The GH secretagogues had no effect on these age-related changes. However, mitogen-induced proliferation of splenic lymphocytes which was decreased in the older rats administered saline was signifi cantly increased in CD4(+) lymphocytes obtained from older rats admini stered GHRH and GHRP. Proliferation was not affected by administration of GH secretagogues to the younger rats. The results of this study sh ow that endogenous GH was effective in completely reversing the effect of aging on thymic weight loss while partially changing certain aspec ts of lymphocyte differentiation and proliferation. The differential r esponses suggest that endogenous GH has selective actions on distinct elements of the immune system.