The experiments reported herein were conducted to determine how corticosterone regulates growth and plasma insulin-like growth factor (IGF) I and IGF-binding protein (IGFBP) concentrations in normal and streptozotocin (STZ)-induced diabetic rats. Males were bilaterally adrenalectomized (Ax) or sham Ax and given intravenous injections of 0, 30, or 65 mg STZ per kg body wt (0, 30, or 65 STZ) to induce varying degrees of insulin deficiency and implanted with 100-mg pellets containing 0, 40, or 80% corticosterone in cholesterol. Changes in plasma IGFBP concentrations were determined by Western ligand blotting or immunoblots. Neither IGFBP-5 nor IGFBP-6 was detected in anyof the treatment groups. Plasma IGFBP-2 was elevated and IGF-I was reduced in the nondiabetic Ax rats compared with sham Ax controls, but plasma IGFBP-3 and -4 were not significantly changed. Adrenalectomy had no affect on tibial growth or plasma IGFBP-1 in these animals. Plasma IGF-I, IGFBP-1and -3, and tibial growth were equal among 0, 30, and 65 STZ Ax rats that did not receive corticosterone. Plasma IGFBP-4 was inversely related to the amount of STZ injected in these animals, and IGFBP-2 was elevated in those given the high dose of STZ. In the 0 STZ Ax rats, plasma IGF-I and IGFBP-3 increased in proportion to the corticosterone implant dose, but IGFBP-1 was unaffected. By contrast, IGF-I and IGFBP-3 were unaltered by corticosterone in the 30 STZ Ax rats, and IGFBP-1 increased in proportion with the dose of corticosterone. In the 65 STZ rats given 40% corticosterone, IGFBP-3 was elevated, but IGF-I was not changed. However, both of these parameters were reduced considerably in the 80% corticosterone rats. Plasma IGFBP-1 increased in direct proportion to the corticosterone implant dose in the 30 and 65 STZ rats but was relatively unchanged inthe 0 STZ rats. These results indicate that elevated corticosterone production is largely responsible for the reduced growth and changes in plasma concentrations of IGF-I and IGFBPs associated with IDDM. Plasma IGF-I and tibial growth are normally correlated in nondiabetic rats but were not inthe corticosterone-treated animals; thus, corticosterone contributes to IGF-I resistance in vivo. The effect of corticosterone on the plasma IGFBPs was most striking in the insulin-deficient rats, suggesting that the ability of corticosterone to modify circulating concentrations of IGFBPs is enhanced by insulin deficiency. The rise in plasma IGFBP-1 and the reduction in IGFBP-4 in rats withIDDM is due in part to corticosterone. However, IGFBP-2 was reduced to nearly nondetectable levelsby both doses of corticosterone. The rise in IGFBP-2 in the Ax 65 STZ rats and the decrease in IGFBP-4 in both groups of STZ-injected Ax rats not given corticosterone appears to be due to insulin deficiency per se, rather than to corticosterone. In all groups, plasma IGFBP-4 and tibial growth were inversely related to the corticosterone implant dose, suggesting that IGFBP-4 may have a growth-promoting role in vivo.

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