Effects of insulin-like growth factor I on growth and polyamine metabolism in various organs in rats.

BACKGROUND/AIM: Human insulin-like growth factor I (IGF-I) is known to be the mediator of growth hormone dependent proliferation and is responsible for growth-promoting effects in the gastrointestinal tract. Polyamines play an essential role in cell growth and differentiation. The aim of the present study was to investigate the growth-promoting potency of IGF-I in various organ systems simultaneously in rats and the potential role of the polyamine metabolism during IGF-I-induced gastrointestinal growth.

METHODS

Based on results of initial dose-response studies, male Wistar rats (150 g) were either treated by subcutaneous injections with (1) IGF-I (1 x 1,000 microg/kg/24 h); (2) IGF-I plus alpha-difluoromethylornithine (3 x 300 mg i.p./kg/24 h plus 2% in drinking water), a specific inhibitor of intracellular polyamine de novo synthesis, or (3) saline (controls). 9-10 animals per group were sacrificed after 5 days of treatment.

RESULTS

IGF-I caused a significant (p < 0.005) increase in the weight of small intestine and spleen due to hyperplasia in the small intestine and hypertrophy and hyperplasia in the spleen, while no trophic effects could be observed in stomach or pancreas. The amylase concentration in the pancreas was increased. Simultaneously administered alpha-difluoromethylornithine significantly (p < 0.005) abolished the IGF-I-induced trophic effects in small intestine and spleen.

CONCLUSIONS

These data reveal different trophic effects of IGF-I in various organ systems: while significant growth stimulation was found in small intestine and spleen, no proliferation was seen in pancreas and stomach. Polyamines obviously play an important role in IGF-I-mediated gastrointestinal growth.