DIFFERENTIAL TISSUE REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I CONTENT AND BINDING-PROTEINS AFTER ENDOTOXIN

The purpose of the present study was to investigate the regulation of plasma and tissue levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-1, -2, and -3 (IGFBP-1, -2, and -3) in rats injected with Escherichia coli lipopolysaccharide (LPS), a component of the outer cell wall of gram-negative bacteria. When injected iv into conscious, overnight fasted rats, plasma IGF-I levels were initially decreased within 1 h, maximally depressed at 4 h, and still only 35-45% of control values at 24 h. GH levels were reduced as early as 30 min after LPS, averaged 80-90% of control values between 1-4 h, but had returned to basal levels by 24 h. The magnitude and duration of these changes were similar regardless of whether 100 or 10 mug/100 g BW (LD20 and LD0, respectively) LPS were injected. Plasma levels of IGFBP-1 and a 28K mol wt BP (BP-28K) were elevated 2- to 3-fold 4 h after LPS treatment, whereas IGFBP-3 and -2 levels were unchanged. The elevation in plasma IGFBP-1 and IGFBP-28K was observed as early as 1 h and was sustained for up to 24 h after LPS treatment. IGF-I levels were decreased 30-50% in liver, pituitary, and skeletal muscle, unchanged in brain, and elevated 5-fold in kidney in response to LPS. Of the tissues sampled, IGFBP-3 and -2 were selectively elevated in liver after LPS treatment. IGFBP-1 was increased in liver, muscle, and kidney in response to LPS. The level of the 28,000 mol wt BP was increased in liver (83%) and not changed in muscle or brain. These data indicate that LPS produces both rapid and sustained alterations in circulating levels of GH, IGF-I, and IGFBPs. Furthermore, there were marked tissue-specific changes in levels of IGF-I and IGFBPs. LPS-induced changes in plasma and tissue IGFBP-3 were not regulated by changes in GH, and changes in insulin could not explain the alterations in IGFBP-1 and -2. These results suggest that after the injection of LPS, changes in IGF-I and IGFBP levels are regulated by a mechanism(s) different from those previously described.