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 intestine. However, it is not known whether this represents an alternative developmental pathway or is essentially an advancement of normal ontogeny. The goal of the present study was to address this question using the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU), which is known to selectively inhibit differentiation in a number of tissues. Intestinal 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 occurs continuously along the crypt-villus axis. After administration of BrdU to suckling and mature animals, there was no effect on lactase and sucrase activities, respectively. Thus BrdU does not inhibit crypt-villus differentiation in either the suckling or mature jejunum. In the second experiment, dexamethasone was used to induce precocious maturation in the rat jejunum on day 10. BrdU treatment significantly inhibited glucocorticoid-induced elevation of sucrase, trehalase, and glucoamylase but had no effect on the lactase activity. In contrast, treatment with BrdU during normal development significantly accelerated the ontogenic rise of sucrase and trehalase as well as the ontogenic decline of lactase. The acceleration of development was also seen in adrenalectomized 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 maturation suggests that such maturation involves different molecular mediators than normal ontogeny.
Department of Biology, University of Houston 77204-5513.
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Nanthakumar
S J
SJ
Henning
D000315:Adrenalectomy; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling / Q000254:growth & development; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002454:Cell Differentiation; D005938:Glucocorticoids / Q000494:pharmacology*; D007422:Intestines / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D000520:alpha-Glucosidases / Q000378:metabolism
D005938:Glucocorticoids; D000520:alpha-Glucosidases; D001973:Bromodeoxyuridine