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Premature expression of sucrase-isomaltase triggered by corticoid-dependent changes in polyamine metabolism
E Nsi-Emvo1, B Chaton, C Foltzer-Jourdainne
1Department of Nutritional Therapy, Hôpitaux Universitaires, Strasbourg, France.
Insights
Starvation and glucocorticoids trigger premature intestinal sucrase-isomaltase (SI) expression in rats. This precocious development is linked to ornithine decarboxylase (ODC) and polyamine metabolism changes.
Area of Science:
- Gastroenterology
- Developmental Biology
- Molecular Endocrinology
Background:
- Intestinal sucrase-isomaltase (SI) expression typically matures post-weaning.
- Glucocorticoids and polyamine metabolism are implicated in intestinal development.
Purpose of the Study:
- To investigate the link between corticoid-induced premature SI expression and polyamine metabolism in preweaned rats.
- To elucidate the role of ornithine decarboxylase (ODC) in this process.
Main Methods:
- Induction of precocious SI expression via starvation or hydrocortisone (HC) administration in preweaned rats.
- Assessment of SI mRNA and activity, corticosterone levels, and ODC expression.
- Pharmacological inhibition of ODC using alpha-difluoromethylornithine (DFMO) and blockade of glucocorticoid receptors with RU-38486.
Main Results:
- Starvation at postnatal day 12 induced precocious SI expression, associated with increased corticosterone and ODC expression.
- RU-38486 blocked starvation-induced ODC stimulation and SI mRNA increase.
- HC administration increased ODC mRNA, and co-administration with RU-38486 or DFMO reduced SI mRNA and activity.
Conclusions:
- Premature induction of intestinal SI expression is dependent on changes in ODC expression and polyamine metabolism.
- Both endogenous hormonal changes and exogenous glucocorticoids can elicit these metabolic shifts, leading to precocious SI development.
Abstract:
A possible link between the corticoid-elicited premature expression of intestinal sucrase-isomaltase (SI) and endogenous changes in polyamine metabolism was investigated in preweaned rats. Starvation at postnatal day 12 caused a precocious expression of SI mRNA and activity. A rapid upsurge of serum corticosterone was observed during the first hour of isolation, occurring in parallel with a transient enhancement of ornithine decarboxylase (ODC) expression and followed by an increase in mucosal polyamine content. Administration of the antiglucocorticoid RU-38486 completely prevented the starvation-evoked stimulation of ODC. The treatment of the sucklings with RU-38486 or with alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC, dramatically reduced the amount of SI mRNA. When exogenous hydrocortisone (HC) was administered to 12-day-old sucklings nourished by their dam, an important accumulation of ODC mRNA was observed in the intestinal mucosa 4 h after treatment. Sucklings receiving HC and treated concomitantly with either RU-38486 or DFMO exhibited a reduced amount of ODC mRNA and a dramatic decline in both SI mRNA and activity. Altogether these data support the view that the premature induction of SI expression is dependent on changes in ODC expression and polyamine metabolism that can be elicited either by endogenous changes or by exogenously administered glucocorticoids.