DISTINGUISHING NORMAL AND GLUCOCORTICOID-INDUCED MATURATION OF INTESTINE USING BROMODEOXYURIDINE

Exogenous glucocorticoids administered during the first two postnatal weeks are capable of eliciting precocious maturation of the rat intest ine. However, it is not known whether this represents an alternative d evelopmental pathway or is essentially an advancement of normal ontoge ny. The goal of the present study was to address this question using t he thymidine analogue 5-bromo-2'-deoxyuridine (BrdU), which is known t o selectively inhibit differentiation in a number of tissues. Intestin al development was assessed by following changes in sucrase, trehalase , glucoamylase, and lactase activities. The first experiment assessed whether BrdU has any influence on the cellular differentiation that oc curs continuously along the crypt-villus axis. After administration of BrdU to suckling and mature animals, there was no effect on lactase a nd sucrase activities, respectively. Thus BrdU does not inhibit crypt- villus differentiation in either the suckling or mature jejunum. In th e second experiment, dexamethasone was used to induce precocious matur ation in the rat jejunum on day 10. BrdU treatment significantly inhib ited glucocorticoid-induced elevation of sucrase, trehalase, and gluco amylase but had no effect on the lactase activity. In contrast, treatm ent with BrdU during normal development significantly accelerated the ontogenic rise of sucrase and trehalase as well as the ontogenic decli ne of lactase. The acceleration of development was also seen in adrena lectomized rats, indicating that it is the glucocorticoid-independent component of normal intestinal ontogeny that is activated by BrdU. The opposite effect of BrdU on glucocorticoid-induced precocious maturati on suggests that such maturation involves different molecular mediator s than normal ontogeny.