The Journal of Experimental Medicine
Rockland Immunochemicals for Research
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Published online 21 August 2006 doi:10.1084/jem.20060357
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 9, 2057-2062
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BRIEF DEFINITIVE REPORT

 The nuclear receptor LRH-1 critically regulates extra-adrenal glucocorticoid synthesis in the intestine

Matthias Mueller1, Igor Cima1, Mario Noti1, Andrea Fuhrer1, Sabine Jakob1, Laurent Dubuquoy2, Kristina Schoonjans2, and Thomas Brunner1

1 Division of Immunopathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland
2 Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), ULP, 67404 Illkirch, France

CORRESPONDENCE Thomas Brunner: tbrunner{at}pathology.unibe.ch

The nuclear receptor liver receptor homologue-1 (LRH-1, NR5A2) is a crucial transcriptional regulator of many metabolic pathways. In addition, LRH-1 is expressed in intestinal crypt cells where it regulates the epithelial cell renewal and contributes to tumorigenesis through the induction of cell cycle proteins. We have recently identified the intestinal epithelium as an important extra-adrenal source of immunoregulatory glucocorticoids. We show here that LRH-1 promotes the expression of the steroidogenic enzymes and the synthesis of corticosterone in murine intestinal epithelial cells in vitro. Interestingly, LRH-1 is also essential for intestinal glucocorticoid synthesis in vivo, as LRH-1 haplo-insufficiency strongly reduces the intestinal expression of steroidogenic enzymes and glucocorticoid synthesis upon immunological stress. These results demonstrate for the first time a novel role for LRH-1 in the regulation of intestinal glucocorticoid synthesis and propose LRH-1 as an important regulator of intestinal tissue integrity and immune homeostasis.

I. Cima's present address is Institute of Cell Biology, ETH Hoenggerberg, 8093 Zurich, Switzerland.

A. Fuhrer's present address is Institute of Physiology, University of Zurich, 8057 Zurich, Switzerland.


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