This proposal attempts to address three outstanding issues in our knowledge regarding intestinal development in the rat. The first issue is the absorption of milk calcium by the suckling animal. All previous studies of the development of Ca absorption have used simple Ca salts. However, in both human and bovine milk a large proportion of the Ca is protein bound. We will first determine whether the same is true in rat milk and, assuming positive results, will study the absorption of Ca in its bound form. The hypotheses are that this Ca will be absorbed by pinocytosis in the ileum; that this mode of absorption will decline at the time of weaning; and that it will be influenced by both glucocorticoids and vitamin D. Ca absorption will be measured in intact rat pups using Ca45-labelled milk given intragastrically or placed directly in ligated segments of the duodenum, jejunum and ileum. We will also determine whether milk Ca remains protein bound in the lumen of the gastrointestinal tract and in the mucosa following absorption. The second issue is the understanding of what causes the developmental surge of circulating corticosterone which occurs in the rat in the third postnatal week. We are proposing that it is due to decreased removal of corticosterone from the bloodstream rather than to increased production by the adrenal, and that the decreased removal is the result of increased binding to corticosteroid-binding globulin (CBG). We will directly test these ideas by measuring the developmental changes of the following parameters for corticosterone: virtual volume of distribution, half-life, metabolic clearance rate, and secretion rate. The role of CBG in any changes of these parameters will be assessed by repeating the measurements for the synthetic glucocorticoid, dexamethasone, which does not bind to CBG. The third issue is the molecular mechanisms underlying enzyme changes in the developing intestine. As a reasonable beginning to this new field of endeavor, we have proposed to construct a recombinant DNA library complementary to large poly(A)+RNA2 of adult intestine using the Lambdagtll vector; to screen this library for portions of the gene encoding sucrase-isomaltase (SI); to use this cloned SI DNA to make a probe which will be used to quantitate SI mRNA during the development; to measure the rate of transcription of SI mRNA by nuclei isolated from rat pups of various ages; and finally, to determine whether developmental changes in the quantity of SI mRNA and the rates of its transcription are under glucocorticoid control.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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General Medicine A Subcommittee 2 (GMA)
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University of Houston
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Yaylaoglu, Murat B; Agbemafle, Barbara M; Oesterreicher, Thomas J et al. (2006) Diverse patterns of cell-specific gene expression in response to glucocorticoid in the developing small intestine. Am J Physiol Gastrointest Liver Physiol 291:G1041-50
Agbemafle, Barbara M; Oesterreicher, Thomas J; Shaw, Chad A et al. (2005) Immediate early genes of glucocorticoid action on the developing intestine. Am J Physiol Gastrointest Liver Physiol 288:G897-906
Oesterreicher, Thomas J; Henning, Susan J (2004) Rapid induction of GATA transcription factors in developing mouse intestine following glucocorticoid administration. Am J Physiol Gastrointest Liver Physiol 286:G947-53
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Gartner, Hans; Shukla, Pramila; Markesich, Diane C et al. (2002) Developmental expression of trehalase: role of transcriptional activation. Biochim Biophys Acta 1574:329-36
Oesterreicher, T J; Markesich, D C; Henning, S J (2001) Cloning, characterization and mapping of the mouse trehalase (Treh) gene. Gene 270:211-20
Solomon, N S; Gartner, H; Oesterreicher, T J et al. (2001) Development of glucocorticoid-responsiveness in mouse intestine. Pediatr Res 49:782-8
Henning, S J; Oesterreicher, T J; Osterholm, D E et al. (1999) Meprin mRNA in rat intestine during normal and glucocorticoid-induced maturation: divergent patterns of expression of alpha and beta subunits. FEBS Lett 462:368-72
Oesterreicher, T J; Leeper, L L; Finegold, M J et al. (1998) Intestinal maturation in mice lacking CCAAT/enhancer-binding protein alpha (C/EPBalpha). Biochem J 330 ( Pt 3):1165-71
Oesterreicher, T J; Nanthakumar, N N; Winston, J H et al. (1998) Rat trehalase: cDNA cloning and mRNA expression in adult rat tissues and during intestinal ontogeny. Am J Physiol 274:R1220-7

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