This Article Full Text Full Text (PDF) All Versions of this Article: 148/3/1445    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mueller, M. Articles by Brunner, T. Search for Related Content PubMed PubMed Citation Articles by Mueller, M. Articles by Brunner, T.

Differential Regulation of Glucocorticoid Synthesis in Murine Intestinal Epithelial Versus Adrenocortical Cell Lines

Division of Immunopathology (M.M., A.A., I.C., N.C., T.B.), Institute of Pathology, University of Bern, 3010 Bern, Switzerland; and Institut de Génétique et de Biologie Moléculaire et Cellulaire (K.S.), Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, 67404 Illkirch, France

Address all correspondence and requests for reprints to: Thomas Brunner, Division of Immunopathology, Institute of Pathology, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland. E-mail: tbrunner{at}pathology.unibe.ch.

Glucocorticoids are steroid hormones with important functions in development, immune regulation, and glucose metabolism. The adrenal glands are the predominant source of glucocorticoids; however, there is increasing evidence for extraadrenal glucocorticoid synthesis in thymus, brain, skin, and vascular endothelium. We recently identified intestinal epithelial cells as an important source of glucocorticoids, which regulate the activation of local intestinal immune cells. The molecular regulation of intestinal glucocorticoid synthesis is currently unexplored. In this study we investigated the transcriptional regulation of the steroidogenic enzymes P450 side-chain cleavage enzyme and 11ß-hydroxylase, and the production of corticosterone in the murine intestinal epithelial cell line mICcl2 and compared it with that in the adrenocortical cell line Y1. Surprisingly, we observed a reciprocal stimulation pattern in these two cell lines. Elevation of intracellular cAMP induced the expression of steroidogenic enzymes in Y1 cells, whereas it inhibited steroidogenesis in mICcl2 cells. In contrast, phorbol ester induced steroidogenic enzymes in intestinal epithelial cells, which was synergistically enhanced upon transfection of cells with the nuclear receptors steroidogenic factor-1 (NR5A1) and liver receptor homolog-1 (NR5A2). Finally, we observed that basal and liver receptor homolog-1/phorbol ester-induced expression of steroidogenic enzymes in mICcl2 cells was inhibited by the antagonistic nuclear receptor small heterodimer partner. We conclude that the molecular basis of glucocorticoid synthesis in intestinal epithelial cells is distinct from that in adrenal cells, most likely representing an adaptation to the local environment and different requirements.

This article has been cited by other articles:

				P. Ye, C. J Kenyon, S. M MacKenzie, K. Nichol, J. R Seckl, R. Fraser, J. M C Connell, and E. Davies Effects of ACTH, dexamethasone, and adrenalectomy on 11{beta}-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the rat central nervous system J. Endocrinol., February 1, 2008; 196(2): 305 - 311. [Abstract] [Full Text] [PDF]