EFFECTS OF STREPTOZOTOCIN TREATMENT IN GROWTH-HORMONE (GH) AND GH ANTAGONIST TRANSGENIC MICE

To investigate GH's role in diabetic end organ damage, experimental di abetes was induced with streptozotocin (STZ) in bovine GH (bGH) or bGH antagonist transgenic mice and in their nontransgenic (NTG) litter ma tes. Body growth, blood glucose, serum insulin-like growth factor-I le vels, liver GH receptor (GHR) binding, and kidney histology of these a nimals were evaluated. After administration of multiple low doses of S TZ, 90% of the mice developed hyperglycemia. The diabetic animals, esp ecially those expressing GH and GH antagonist transgenes, demonstrated retarded body growth and reduced insulin-like growth factor-I levels when compared with their nondiabetic litter mates. Kidney histology re vealed severe glomerulosclerosis in diabetic and nondiabetic bGH trans genic mice. Diabetic NTG mice exhibited moderate kidney lesions. Diabe tic bGH antagonist transgenic mice possessed normal glomeruli indistin guishable from those seen in nondiabetic NTG mice. GHR-binding assays revealed that liver GHR-binding sites were significantly reduced in di abetic NTG mice and transgenic dwarf mice when compared with their non diabetic controls. Conversely, liver GHR-binding ability was significa ntly increased in bGH transgenic mice as compared with their NTG litte rmates and remained high during diabetes. It is concluded that transge nic mice that express a GH antagonist are protected from diabetes and or GH-induced nephropathy.