Effect of epidermal growth factor on insulin-like growth factor-I (IGF-I) and IGF-binding protein synthesis by adult rat hepatocytes.

Growth hormone has been established as a primary regulator of IGF-I gene expression in adults, not only in liver but also in many extrahepatic tissues. We considered the possibility that IGF-I production by adult rat liver could also be stimulated by epidermal growth factor (EGF), a peptide known to be involved in liver regeneration. Chromatographic analysis performed after acid treatment of conditioned media revealed the presence of both immunoreactive (IR) IGF-I and IGF binding protein (IGFBP). Both IR IGF-I and IGFBP were present in the conditioned medium of adult rat hepatocytes in basal conditions. The stimulation of IGF-I and IGFBP secretion by EGF appears to be dose-dependent with a significant increment already evident at 5 nM. That EGF stimulates secretion is supported by the finding that IGF-I and IGFBP-1 mRNA levels are increased after EGF supplementation. We conclude that adult rat hepatocytes spontaneously produce IGF-I and IGFBP, and that EGF is able to increase their synthesis and secretion. This non-growth hormone-dependent regulation of IGF-I and IGFBP-1 production by adult rat hepatocytes in culture indicates an important autocrine/paracrine role for IGF-I, particularly during liver regeneration after extensive organ mass loss.

Insulin-like growth factor-I (IGF-I) and IGF-I binding protein in the follicular fluids of growth hormone treated patients.

The presence of GH, insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), oestradiol (E2) and progesterone (PG) were investigated in the fluids obtained from various ovarian follicles of seven patients in whom the induction of super-ovulation was achieved only after GH (0.1 U/kg BW/day) was added to the gonadotrophin therapy. The follicular fluids of six patients responsive to treatment with gonadotrophin alone served as a control. In patients treated with combined therapy, the results demonstrated the presence in the follicular fluids of GH (M +/- SEM: 8.5 +/- 0.6 mU/l), E2 (771 +/- 38 nmol/l), and PG (16.4 +/- 0.7 pmol/l) in significantly higher concentrations compared to that in control follicles (6.2 +/- 0.8 mU/l, 681 +/- 30 nmol/l, and 14.4 +/- 0.6 pmol/l; P = 0.002, 0.012, 0.0001 respectively). Acid-extractable IGF-I (143 +/- 9 ng/ml) and EGF (3.9 +/- 0.3 ng/ml) concentrations were similar to those of control fluids (124 +/- 10 ng/ml and 2.9 +/- 0.7 ng/ml respectively) and were highly correlated with each other (P less than 0.001), suggesting a stimulatory effect of EGF on the local IGF-I production. A correlation between GH and IGF-I (n = 51, r = 0.36), as well as between IGF-I and PG (n = 48, r = 0.77) and E2 (n = 48, r = 0.55) was evident only in the follicular fluid of GH-treated subjects.(ABSTRACT TRUNCATED AT 250 WORDS)