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

Mueller, Matthias; Cima, Igor; Noti, Mario; Fuhrer, Andrea; Jakob, Sabine; Dubuquoy, Laurent; Schoonjans, Kristina; Brunner, Thomas (2006). The nuclear receptor LRH-1 critically regulates extra-adrenal glucocorticoid synthesis in the intestine. Journal of experimental medicine, 203(9), pp. 2057-62. New York, N.Y.: Rockefeller University Press 10.1084/jem.20060357

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Brunner, Thomas

ISSN:

0022-1007

ISBN:

16923850

Publisher:

Rockefeller University Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:48

Last Modified:

06 Dec 2013 13:42

Publisher DOI:

10.1084/jem.20060357

PubMed ID:

16923850

Web of Science ID:

000240288000009

URI:

https://boris.unibe.ch/id/eprint/19917 (FactScience: 2994)

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