Development of glucocorticoid-responsiveness in mouse intestine.
There are conflicting data from human studies regarding the ability of exogenous glucocorticoids to stimulate maturation of the small intestine. The discrepancies may relate to differences in hormone doses and age administered. To explore this general concept, we have used a mouse model to determine intestinal responsiveness to dexamethasone (DEX) at various times during development. We first showed that trehalase mRNA is a sensitive marker of intestinal maturation in the mouse; being undetectable (by Northern blotting) in the prenatal period, expressed at low levels during the first 2 postnatal weeks and then displaying a marked increase in the 3rd postnatal week. DEX was unable to elicit detectable trehalase mRNA in fetal mice, but caused significant increases in the postnatal period. The use of a range of DEX doses (0.0125-2.5 nmol/g BW per day) established that there is no change in sensitivity between the 1st and 2nd postnatal weeks, but there is a significant increase in maximal responsiveness of trehalase mRNA to the hormone. Similar results were obtained when sucrase-isomaltase mRNA was assayed in the same animals. Thus, in this rodent model, there appears to be at least three phases in the DEX responsiveness of the developing intestine: an early phase (prenatal) when DEX is unable to elicit intestinal maturation; then a phase (first postnatal week) of modest responsiveness; then a transition to increased responsiveness. These findings point to the need for careful attention to dose and age in analyses of glucocorticoid effects in human infants.
Solomon
N S
NS
Departments of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Gartner
H
H
Oesterreicher
T J
TJ
Henning
S J
SJ
D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects* / Q000196:embryology* / Q000201:enzymology / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013394:Sucrase-Isomaltase Complex / Q000235:genetics; D014198:Trehalase / Q000235:genetics
D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D013394:Sucrase-Isomaltase Complex; D014198:Trehalase