PRETREATMENT WITH BOVINE GROWTH-HORMONE IS AS EFFECTIVE AS TREATMENT DURING METABOLIC STRESS TO REDUCE CATABOLISM IN FASTED LAMBS

The effects of recombinant bovine GH (rbGH) treatment on the insulin-l ike growth factor (IGF) axis and protein metabolism during fasting ind uced metabolic stress were evaluated in young lambs. To explore whethe r rbGH pretreatment alone might offer a degree of protection against n utritional stress, we compared the effects of rbGH given only before o r during the fasting-induced metabolic stress with that given over the whole period. The animals were fed ad libitum for 5 days (well fed ph ase) and then fasted for 70 h (fasted phase). The rbGH was administere d during either the well fed and the fasted phase (G-G), only during t he well fed phase (G-S), or only during the fasted phase (S-G), and th e effects were compared with those of saline treatment throughout both phases (S-S; n = 7/group). The rate of net protein catabolism, analyz ed on the final day of the study, was reduced (P < 0.001) to a similar degree in all rbGH-treated groups compared with that in the S-S group . rbGH pretreatment was as effective as rbGH administered during the c atabolic phase. Plasma IGF-I was increased (P < 0.001) in the well fed phase by rbGH treatment and decreased in the fasted phase in all grou ps. The rbGH treatment during the fasted phase resulted in a smaller f all in plasma IGF-I levels than saline treatment (P < 0.05, G-G vs. G- S and S-G us. S-S), but no difference was observed in the specific bin ding of [I-125]ovine GH to the hepatic membranes from animals of the d ifferent groups. There was a negative correlation between net protein catabolism and plasma IGF-I levels (r = -0.48; P < 0.01) and specific binding of [I-125]ovine GH to hepatic membranes (r = -0.56; P < 0.001) . Plasma IGF-II levels were decreased by rbGH treatment during the wel l fed phase, but the responses to treatment during the fasted phase we re variable, suggesting that plasma IGF-II is regulated in a different manner than plasma IGF-I. The fasting-induced fall (P < 0.05) in plas ma concentrations of IGF-binding protein (IGFBP)-3 was reduced with rb GH treatment, and plasma concentrations of IGFBP-2 were altered in an inverse manner. This study suggests that fasting-induced GH resistance can be alleviated by rbGH treatment independent of whether treatment is commenced before or after the onset of catabolic stress. Our observ ation of prolonged anticatabolic action of prophylactic rbGH treatment supports the proposal that prophylactic use of GH may reduce the degr ee of catabolism associated with subsequent interventions and, thus, i mprove clinical outcome.