Glucocorticoids have pleiotropic effects on small intestinal crypt cells.
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 p27(Kip1). 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.
Quaroni
A
A
Section of Physiology, Cornell University, Ithaca, New York 14853, USA. aq10@cornell.edu
Tian
J Q
JQ
Göke
M
M
Podolsky
D K
DK
D000469:Alkaline Phosphatase / Q000378:metabolism; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000737:chemistry; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis; D003599:Cytoskeleton / Q000187:drug effects; D003600:Cytosol / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D007421:Intestine, Small / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects*; D008247:Lysosomes / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D008871:Microvilli / Q000201:enzymology; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011987:Receptors, Steroid / Q000502:physiology; D013394:Sucrase-Isomaltase Complex / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects; D014316:Tritium; D025521:Tumor Suppressor Proteins; D000520:alpha-Glucosidases / Q000378:metabolism
D000728:Androgens; D001426:Bacterial Proteins; C493958:Cdkn1a protein, rat; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D005938:Glucocorticoids; D008869:Microtubule-Associated Proteins; D011987:Receptors, Steroid; D025521:Tumor Suppressor Proteins; D014316:Tritium; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011374:Progesterone; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D013394:Sucrase-Isomaltase Complex; C112179:sucrase-isomaltase-maltase; D000520:alpha-Glucosidases; D006854:Hydrocortisone