STUDIES ON THE MATURATION OF THE SMALL-INTESTINE IN THE FETAL SHEEP .2. THE EFFECTS OF EXOGENOUS CORTISOL

The effect of cortisol on small intestinal maturation was investigated in catheterized fetal sheep by infusing 2 mg cortisol/d between 105 and 115 d gestation (term ca. 147 d). This treatment resulted in a fivefold increase in plasma cortisol compared with catheterized control fetuses of the same age. There were no detectable changes in enterocyte morphology after the cortisol infusion; the size and density of most intestinal components were largely unaffected by the treatment. By contrast, the kinetics of the enterocyte population were significantly altered by the raised cortisol levels. The proportion of crypt cells labeled was significantly increased from 0.20 .+-. 0.04 to 0.33 .+-. 0.03 in the proximal region ((P < 0.01) and from 0.22 .+-. 0.03 to 0.31 .+-. 0.02 in the distal region (P < 0.01). The migration of enterocytes in both regions was significantly increased to nearly twice the control values (P < 0.05). Correspondingly, renewal time was almost halved in both regions, while cell density was unchanged in distal and decreased in proximal regions. Hence cell loss appeared to have increased as a result of the cortisol infusion. The kinetic parameters for the villus enterocyte population of the fetuses receiving cortisol before 115 d were of similar magnitude to those previously seen in the normal near-term fetus. To this extent exogenous cortisol treatment given before a pre-partum surge mimicked the action of the endogenous hormone in late gestation.