EPIDERMAL GROWTH-FACTOR PRIMES INTESTINAL EPITHELIAL-CELLS FOR PROLIFERATIVE EFFECT OF INSULIN-LIKE GROWTH-FACTOR-I

Insulin-like growth factor I (IGF-I) synergistically enhances epiderma l growth factor (EGF) -stimulated proliferation of intestinal epitheli al cells. A possible mechanism of this synergy is that EGF acts as a ' 'competence'' factor increasing the fraction of proliferating cells by promoting transition from G(0) to G(1), thus allowing IGF-I, a ''prog ression'' factor, to act as a proliferative agent on the cycling popul ation. Consistent with this hypothesis would be temporally distinct ac tions wherein initial brief exposure to EGF would permit synergy, wher eas pretreatment with IGF-I would not. Rat intestinal epithelial cells of the IEC-18 crypt cell line were serum-deprived, then treated with EGF (5 x 10(-9) M), IGF-I (5 x 10(-9) M), or insulin (2 x 10(-6) M) fo r a 30-min pulse and then media containing EGF, IGF-I, insulin, or no factor was substituted for 48 hr. IGF-I and EGF each stimulated entero cyte proliferation; together they synergistically promoted cell growth . A brief pulse of IGF-I neither induced cell proliferation nor enhanc ed the EGF effect. Initial brief exposure to EGF, however, was equally efficacious as continuous exposure and allowed full synergy with IGF- I. Insulin at supraphysiologic levels acted similarly to IGF-I. Thus, EGF acted as a competence factor priming the cells for subsequent acti on by IGF-I. The cell kinetic parameters of these growth factors may b e important to both physiologic and pathologic enterocyte growth regul ation.