Growth hormone stimulates bone marrow and thymic reconstitution in aged rats

The age-associated dysregulation in immunologie function is related to a decline in plasma growth hormone (GH) and its growth-promoting peptide insulin-like growth factor-I (IGF-I). We recently demonstrated that IGF-I inhibits apoptosis in murine myeloid progenitor cells in vitro (J. Immunol. 156:939, 1996), suggesting that GH or IGF-I may play a role in maintaining hematopoietic tissues in the aged. In the present study, GH-secreting pituitary GH, cells were implanted into 22-month-old female Wistar-Furth rats for eight weeks. We compared tissues from GH, implanted, rHuGH ( 1 mg/kg, bidx28d) and saline-injected control rats. Gross and microscopic observations in aged rats treated with GH, cells or rHuGH included: reconstitution of bone marrow celluiarity, thymic regeneration and extramedullary hematopoiesis with marked splenomegaly. In aged GH,-and rHuGH-treated rats, bone marrow celluiarity increased (400+33% and 200+8%, respectively, p<0.01) as compared to aged controls. The increase in marrow celluiarity was primarily attributed to erythroid and myeloid proliferation, but all lineages were represented. Using an in vitro colony forming assay (250 U/ml rMuIL-3 + 1.25 ng/ml rMuGM-CSF), we found that the number of myeloid progenitors was reduced in aged rats as compared to young controls (54+4 vs 81+3/2xl04 cells, respectively; p<0.01). Treatment of aged rats with either GH, cells or rHuGH effectively reversed the age-associated decline in myeloid progenitors (144+13% and 145+15% compared to aged rats, respectively; p<0.01). These results suggest that GH acts in vivo to promote myeloid, erythroid and lymphoid differentiation and proliferation in aged rats.(NIH Grant AG 06246).