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Am J Physiol Gastrointest Liver Physiol 277: G1027-G1040, 1999;
0193-1857/99 $5.00
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Vol. 277, Issue 5, G1027-G1040, November 1999

Glucocorticoids have pleiotropic effects on small intestinal crypt cells

Andrea Quaroni1, Jean Q. Tian1, Michael Göke2, and Daniel K. Podolsky2

1 Section of Physiology, Cornell University, Ithaca, New York 14853; and 2 Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts 02114

Glucocorticoids have long been known to accelerate maturation of the intestinal tract, but the molecular mechanisms that account for their physiological function in the epithelium remain poorly characterized. Using rat intestinal epithelial cell lines (IEC-6, IEC-17, and IEC-18) as models, we have characterized glucocorticoid receptors in crypt cells and documented striking morphological, ultrastructural, and functional alterations induced by these hormones in intestinal cells. They include arrest of growth, formation of tight junctions, appearance of long, slender microvilli, reorganization of the endoplasmic reticulum and trans-Golgi network, and downregulation of the cell cycle regulatory proteins cyclin-dependent kinase 6 and p27Kip1. These effects are consistent with the activation or modulation of multiple genes important in the physiological function of absorptive villous cells but are probably not directly involved in the induction of cell differentiation.

cell proliferation; steroid receptors; cyclin-dependent kinase inhibitors; p21WAF1/Cip1; p27Kip1


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