The continuing objectives of this research are to elucidate factors which participate in the regulation of intestinal growth and differentiation, and to delineate the regulatory steps at which regulators (or modulators) exert their effects. We propose to use hypophysectomized-artifically reared (HAR) rat pups as an in vivo system to examine hormonal effects on gastric emptying rate, intestinal villus length, crypt depth and epithelial cell proliferation. Autoradiographic techniques will be used to determine cell migration rates. At the same time, intestinal disaccharidase activites will be measured, and the intracellular synthesis, and transport of sucrase-isomaltase will be examined by a comination of biochemical, immunocytochemical and autoradiographic techniques. The realtive effects of hormonal therapy systemic and luminal routes will be determined. To evaluate separately the effects of luminal and systemic factors on intestinal growth, we plan to use an in vivo - in vitro system. The intestine of newborn rats will be transplanted into the subcutaneous layer of syngeneic littermates. Differences in cell proliferation after hormonal therapy between implanted and host intestine will permit us to distinguish luminal factors from systemic factors. We also propose to use primary cultures as an in vitro system to (1) develop optimal conditions for both cell proliferation and phenotype maintenance; (2) determine hormonal effects on cell proliferation and differentiation and (3) examine hormonal effects on the differentiation of specialized intestinal cell types. Attempts will also be made to subculture and propagate epithelial cells. The effect of hydrocortisone and thyroxin on cell proliferation will be examined by flow cytometry. The effect of these hormones on the expression of the sucrase-isomaltase will be determined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK033916-04
Application #
3232328
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1983-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
St. Luke's-Roosevelt Institute for Health Science
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10019
Yeh, K; Yeh, M; Holt, P R et al. (1994) Development and hormonal modulation of postnatal expression of intestinal alkaline phosphatase mRNA species and their encoded isoenzymes. Biochem J 301 ( Pt 3):893-9
Holt, P R; Yeh, K Y (1992) Effects of starvation and refeeding on jejunal disaccharidase activity. Dig Dis Sci 37:827-32
Yeh, K Y; Yeh, M; Montgomery, R K et al. (1991) Cortisone and thyroxine modulate intestinal lactase and sucrase mRNA levels and activities in the suckling rat. Biochem Biophys Res Commun 180:174-80
Yeh, K Y; Yeh, M; Holt, P R (1991) Intestinal lactase expression and epithelial cell transit in hormone-treated suckling rats. Am J Physiol 260:G379-84
Yeh, K Y; Yeh, M; Holt, P R (1991) Thyroxine and cortisone cooperate to modulate postnatal intestinal enzyme differentiation in the rat. Am J Physiol 260:G371-8
Yeh, K Y; Yeh, M; Pan, P C et al. (1991) Posttranslational cleavage of rat intestinal lactase occurs at the luminal side of the brush border membrane. Gastroenterology 101:312-8
Yeh, K Y; Yeh, M; Holt, P R (1989) Induction of rat jejunal epithelial cell expression of sucrase-isomaltase by glucocorticoids in primary cell culture and in vivo. Biol Cell 65:139-50
Yeh, K Y; Yeh, M; Holt, P R (1989) Induction of intestinal differentiation by systemic and not by luminal corticosterone in adrenalectomized rat pups. Endocrinology 124:1898-904
Yeh, K Y; Yeh, M; Holt, P R (1989) Differential effects of thyroxine and cortisone on jejunal sucrase expression in suckling rats. Am J Physiol 256:G604-12