Studies on the Maturation of the Small Intestine in the Fetal Sheep. Ii. The Effects of Exogenous Cortisol

Abstract

SUMMARYThe 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 labelled was significantly increased from 020 +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 < 005). 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 apre-partum surge mimicked the action of the endogenous hormone in late gestation.

The cellular repressor of E1A-stimulated genes mediates glucocorticoid-induced loss of the type-2 IGF receptor in ileal epithelial cells

“…In contrast, we have previously reported a significant increase in ileal epithelial and goblet cell numbers when newborn mice are treated with early postnatal dexamethasone (DEX) (Gordon et al 2001a), suggesting a proliferative mechanism of hypertrophy that is potentially ever present in the neonate. Similar findings have been reported in fetal sheep when exposed to antenatal steroids, indicating that the capacity extends backwards into gestation (Trahair et al 1987). These paradigms have clinical relevance to an emerging and highly morbid neonatal disease known as spontaneous intestinal perforation (also called focal small bowel perforation) which afflicts 5-10% of all extremely low birth weight infants (Garland et al 1999, Gordon et al 1999, Stark et al 2001.…”

The Prenatal Development and Glucocorticoid Control of Brush-Border Hydrolases in the Pig Small Intestine

“…In rodents, it is possible that the glucocorticoid-induced changes in enzyme activity mainly result from increases in enterocyte turnover and replacement of the villus cell population (6,8,35). An increased enterocyte turnover has also been reported in the fetal sheep after cortisol administration (36). However, increased cell proliferation rate in young animals does not always lead to a simultaneous increase in sucrase activity and loss of lactase activity (37,38), and hence other factors must be involved.…”

Perinatal development of the small intestine of the sheep

“…We have furthermore demonstrated that growth of intestinal structures is reduced after fetal bilateral adrenalectomy (Trahair et al, , 1987a. Adrenalectomy also caused a reduction in enterocyte migration, while early cortisol infusion resulted in increases in both the PCL and migration rates (Trahair et al, 1987b). In the sheep fetus the adrenal produces cortisol in response to hypophyseal ACTH from about 120 days onwards (Wintour, 1984).…”