Liver X receptors and cholesterol homoeostasis: spotlight on the adrenal gland.

Liver X receptors and cholesterol homoeostasis: spotlight on the adrenal gland. Research Abstract Details 

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Liver X receptors and cholesterol homoeostasis: spotlight on the adrenal gland. Abstract Text:

C L Cummins,D J Mangelsdorf,

The LXRs (liver X receptors) (LXRalpha and LXRbeta) are nuclear hormone receptors that are activated by oxysterols, endogenous oxidative metabolites of cholesterol. These receptors regulate an integrated network of genes that control whole body cholesterol and lipid homoeostasis. A brief overview of the mechanism of this regulation by LXRs in the liver, macrophage and intestine will be outlined, followed by data from our recent work demonstrating that LXRalpha is crucial in maintaining adrenal cholesterol homoeostasis. In the adrenal gland, oxysterols are formed as intermediates in the conversion of cholesterol into steroid hormones and can act as endogenous activators of LXR. We have found using both gain- and loss-of-function models that LXR acts to maintain free cholesterol below toxic levels in the adrenal gland, through the co-ordinated regulation of genes involved in cholesterol efflux [ABCA1 (ATP-binding-cassette transporter A1)], storage (sterol-regulatory-element-binding protein-1c and apolipoprotein E) and metabolism to steroid hormones (steroidogenic acute regulatory protein). Furthermore, we show that under chronic dietary stress, the adrenal glands of LXR-null mice (and not wild-type mice) accumulate free cholesterol. These results support the role of LXR as a global regulator of cholesterol homoeostasis, where LXR provides a safety valve to limit free cholesterol in tissues experiencing high cholesterol flux.

Liver X receptors and cholesterol homoeostasis: spotlight on the adrenal gland. Publishing Authors By Initials

CL Cummins,DJ Mangelsdorf,

For similar proteins: receptors, cytoplasmic and nuclear research abstracts see: proteins: receptors, cytoplasmic and nuclear research

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Liver X receptors and cholesterol homoeostasis: spotlight on the adrenal gland. Journal Published:

PUBLICATION TYPE: Review

Journal: Biochemical Society transactions

VOLUME: 34

Page Numbers: 1110-3

Journal Abbreviation: Biochem. Soc. Trans.

ISSN: 0300-5127

DAY: 3

MONTH: Dec

YEAR: 2006

Liver X receptors and cholesterol homoeostasis: spotlight on the adrenal gland. Information

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LANGUAGE: eng

NlmUniqueID: 7506897

Liver X receptors and cholesterol homoeostasis: spotlight on the adrenal gland. Keywords Mesh Terms:

KEYWORDS: Receptors, Cytoplasmic and Nuclear

MESH TERMS: physiology

Chemical & Substance for Abstract: Liver X receptors and cholesterol homoeostasis: spotlight on the adrenal gland. Information

Substance Name: Cholesterol

Registry Number: 57-88-5

Grant and Affiliation Information for Liver X receptors and cholesterol homoeostasis: spotlight on the adrenal gland.

AFFILIATION: Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park, Dallas, TX 75390-9050, USA. Carolyn.Cummins@UTSouthwestern.edu

Country: England

AGENCY: United States NIDDK

GRANT: DK62434

ACRONYM: DK

MEDLINETA: Biochem Soc Trans

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