Epidermal growth factor inhibits somatostatin-induced apoptosis

The somatostatin analogue octreotide impairs intestinal regeneration and the adaptive response to intestinal resection by inhibition of enterocyte migration and proliferation and increased apoptosis. Epidermal growth factor (EGF) stimulates regeneration and adaptation by increasing proliferation and reducing apoptosis. The aim of this study was to determine the effect of EGF on octreotide-induced enterocyte apoptosis.

Twenty-four rabbits underwent patch enteroplasty in the distal ileum to stimulate the mucosa. There were four study groups: octreotide 250 microgram/kg/day, EGF 40 microgram/kg/day, EGF plus octreotide, and control. Normal ileal mucosa adjacent to the patch was evaluated at 7 days for villus height, crypt depth, crypt cell production rate (CCPR), and in situ end labeling of DNA fragmentation.

Octreotide alone increased apoptosis compared with controls at the villus tip (40 +/- 7% vs 18 +/- 7%, P < 0.05), lateral villus (9 +/- 2% vs 3 +/- 2%, P < 0.05), and crypt (15 +/- 3% vs 10 +/- 3%, P < 0. 05). EGF decreased apoptosis in the crypt (2 +/- 1%) and villus (6 +/- 1% villus tip and 1 +/- 1% lateral villus, P < 0.05) compartments. EGF inhibited octreotide-induced apoptosis in the crypt (5 +/- 2%) but not the villus (31 +/- 5% villus tip and 6 +/- 2% lateral villus, P < 0.05). Mean DNA fragmentation was significantly greater in octreotide-treated animals (P < 0.05). The octreotide-treated animals had reduced crypt depth and villus height but normal CCPR compared with controls. EGF increased CCPR and crypt depth compared with controls. Combining EGF and octreotide resulted in crypt depth and CCPR similar to those of controls but reduced villus height.

EGF inhibits octreotide-induced apoptosis. This effect is greater in crypt than in villus enterocytes. Octreotide appears to have both direct and indirect effects on enterocyte apoptosis.