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This version published online on September 14, 2006
Molecular Endocrinology, doi:10.1210/me.2006-0187
A more recent version of this article appeared on January 1, 2007
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Submitted on May 4, 2006
Accepted on September 5, 2006

Liver X receptors regulate adrenal steroidogenesis and hypothalamic-pituitary-adrenal feedback

Maria Nilsson, Thomas M. Stulnig, Chin-Yo Lin, Ai Li Yeo, Peter Nowotny, Edison T. Liu, and Knut R. Steffensen*

Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden; Genome Institute of Singapore, 60 Biopolis Street, The Genome, #02-01, Singapore 138672; Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Austria; CeMM - Center of Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria

* To whom correspondence should be addressed. E-mail: knut.steffensen{at}biosci.ki.se.

The nuclear hormone receptors LXR{alpha} (NR1H3) and LXR{beta} (NR1H2) are established regulators of cholesterol, lipid and glucose metabolism and are attractive drug targets for the treatment of diabetes and cardiovascular disease. Adrenal steroid hormones including glucocorticoids and mineralocorticoids are known to interfere with glucose metabolism, insulin signaling and blood pressure regulation. Here we present genome wide expression profiles of LXR responsive genes in both the adrenal and the pituitary gland. LXR activation in cultured adrenal cells inhibited expression of multiple steroidogenic genes and consequently decreased adrenal steroid hormone production. In addition, LXR agonist treatment elevated ACTH mRNA expression and hormone secretion from pituitary cells both in vitro and in vivo. Reduced expression of the glucocortioid-activating enzyme 11{beta}-HSD1 in pituitary cells upon LXR activation suggests blunting of the negative feedback of glucocorticoids by LXRs. In conclusion, LXRs independently interfere with the hypothalamic-pituitary-adrenal-axis (HPA) regulation at the level of the pituitary and the adrenal gland.
Key words: LXR • steroidogenesis • adrenal • HPA-axis

NURSA Molecule Pages Link:

Nuclear Receptors:   LXRβ  |  LXRα
Ligands:   T0901317



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