ALTERATION OF CELLULAR PROLIFERATION IN THE ILEAL EPITHELIUM OF SUCKLING AND WEANED RATS: THE EFFECTS OF ISOPROTERENOL

The purpose of this study was to analyse cell proliferation in the ileum before and after neonatal closure to macromolecules and to determine the effects of the sympathomimetic amine, isoproterenol (IPR), on cell cycle parameters. 8- and 28-day-old rats were employed in this study representing the neonatal periods of pre- and post-closure ileum respectively. The duration of the cell cycle phases was determined by the percentage of labeled metaphases technique (PLM) with computerized analysis of the curves. The generation cycle time was longer in 8-day-old suckling rats (18.63 hr) as compared to the older weaned rats (11.85 hr), and most of this 6.78 hr difference was in the G₁-period (4.5 hr). Other proliferative indices were also lower in the suckling rats—mitotic index (1.9 ± 0.4% as compared to 6.7 ± 0.9%), labelling index (26.8 ± 2.5% versus 44.2 ± 2.6%) and migration rate measured as per cent labeled villus cells (8.9 ± 3.1% versus 45.2 ± 3.4%). IPR was found to inhibit cellular proliferation in the ileal epithelium of both age groups. The cell cycle of the ileal epithelium of 8-day-old rats was lengthened from 18.63 to 21.07 hr and 28-day-old rats from 11.85 to 13.98 hr. IPR produced a decrease in mitotic index from 1.9 ± 0.4% to 1.6 ± 0.4% in pre-closure ileum and from 6.7 ± 0.9% to 5.1 ± 0.6% in post-closure ileum. Labeling index decreased from 26.8 ± 2.5% to 20.0 ± 2.0% in 8-day-old rats and from 44.2 ± 2.6% to 31.1 ± 3.0% in 28-day-old rats after IPR administration. There were also significant differences in growth fraction between age groups and a significant decrease in growth fraction after IPR-treatment. From the results of this study it appears that β-adrenergic stimulation has an inhibitory effect on neonatal ileal epithelium.