Impaired Growth of Small Intestinal Epithelium by Adrenalectomy in Weaning Rats

Abstract

Functional maturation of the small intestine occurs during the weaning period in rats. It is known that this development is facilitated by glucocorticoid. However, the effect of glucocorticoid on morphological development of small intestine has yet to be clarified. The present study evaluated the morphological development and cell proliferation of the small intestine in adrenalectomized (ADX) rat pups. To further understand the mechanism of glucocorticoid effects on intestinal development, we examined the localization of the glucocorticoid receptor in the small intestine. Microscopic analysis showed that growth of villi and crypts is agedependent, and is significantly attenuated in ADX rats compared with sham-operated rats. BrdU-positive cells, i.e. proliferating cells, were primarily observed in crypt compartments and rapidly increased in number during the early weaning period. The increase in BrdUpositive cells could be attenuated by adrenalectomy. The morphological development of small intestine may be associated with increased proliferation of epithelial cells. On the other hand, glucocorticoid receptors were found in epithelial cells of the mid-and lower villi and not in crypts where BrdU-positive cells were localized. These results indicate that the growth of small intestine is attenuated by adrenalectomy, and that glucocorticoid indirectly acts on proliferation of epithelial cells during the weaning period.

Regionalization of pIgR expression in the mucosa of mouse small intestine

“…On the other hand, the higher expression of the gene for GRs in the proximal segment suggests that signaling through this receptor probably is the dominant factor in the upregulation of the expression of pIgR in this region. Taking into account that GC hormones influence a variety of epithelial cell functions in the small intestine by binding to the cytoplasmic GR [44,45], we pose that the higher expression of glucocorticoid receptors in epithelial cells of the proximal segment is an important factor in the higher level of pIgR expression at this site. Finally, food antigens and nutrients, such as vitamin A, abundant in the proximal small intestine, probably contribute to the higher expression of pIgRs in this segment as well [46][47][48].…”

Hydrocortisone induces changes in gene expression and differentiation in immature human enterocytes

“…In vivo, HC treatment of suckling rats increases galactosylation and fucosylation of glycoproteins, which are biochemical markers associated with cellular maturation in the small intestine (4). In addition, the suppression of glucocorticoid secretion by adrenalectomy reduces the level of glycosylation in the small intestine at weaning (22); in vitro, HC induces functional alterations in rat enterocytes, including growth arrest, tight junction formation, microvilli maturation, and reorganization of the endoplasmic reticulum and trans-Golgi network (26). In human studies, Arsenault and Ménard (2) have shown that HC exhibits effects on differentiation and proliferation of fetal small intestinal organ culture, such as brush-border membrane hydrolytic activities (sucrase, lactase, glucoamylase, trehalase, and alkaline phosphatases) and epithelial cell proliferation.…”

Intestinal steroidogenesis

“…Maturation and maintenance of the intestinal epithelial barrier GC mediated effects on the maturation of the small intestine are well recognized both in rodents and humans [47]. For instance, adrenalectomy in rats during the weaning period impairs the mor phological development of the small intestine [48], while injection of cortisone or hydrocortisone to suckling rats increases the expres sion and activity of many small intestinal maturation markers [49 51]. The development of a human intestinal xenograft model demonstrated the responsiveness of the human small intestine to cortisone during the maturation period [52,53].…”