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| Research article summary (published 24 Nov 2008): |
Liver X receptor-alpha regulates proopiomelanocortin (POMC) gene transcription in the pituitary.
Full Abstract
The liver X receptors (LXR-alpha and -beta) are nuclear oxysterol receptors that play pivotal roles in regulating the expression of genes involved in cholesterol transport and metabolism. Recently, several groups have reported that the LXRs also regulate adrenal steroidogenesis. However, the roles of LXRs in the hypothalami-pituitary-adrenal axis, especially whether they regulate proopiomelanocortin (POMC) gene expression in the pituitary, remain to be elucidated. In this report, we demonstrate that LXR mRNA is expressed in the pituitary and that at the protein level, LXR-alpha is dominantly expressed. Next, we show that the LXR agonist TO901317 (TO) increased POMC mRNA levels and the number of cells immunostained with anti-ACTH antibody in the mouse pituitary. We also confirmed that TO elevated plasma ACTH and serum corticosterone levels in vivo and increased the total tissue content of immunoreactive ACTH in the pituitary. TO activated the rat POMC gene promoter (-706/+64 bp) in GH3 and AtT-20 cells. Silencing of LXR-alpha mRNA expression in GH3 cells with small interfering RNA specific to LXR-alpha caused a loss of promoter activity induced by the LXR ligand, suggesting that LXR-alpha directly regulates the POMC gene promoter. EMSAs also demonstrated that the retinoid X receptor-alpha/LXR-alpha heterodimer bound to the region between -73 and -52 bp in the rat POMC gene promoter, and this site was responsible for the induction by TO, as confirmed by chromatin immunoprecipitation assays using AtT-20 cells. Our findings provide the first evidence that LXR-alpha positively regulates the POMC gene promoter at the transcriptional level and suggest LXR-alpha to be a coordinator for cross talk between lipid metabolism and neuroendocrinology.
Author information
Author/s: Matsumoto, Shunichi (S); Hashimoto, Koshi (K); Yamada, Masanobu (M); Satoh, Teturou (T); Hirato, Junko (J); Mori, Masatomo (M);
Affiliation: Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, 3-39-15 Showa-machi Maebashi, Gunma 371-8511, Japan.
Journal and publication information
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Journal: Molecular endocrinology (Baltimore, Md.) (Mol Endocrinol), published in United States. (Language: eng)
Reference: 2009-Jan; vol 23 (issue 1) : pp 47-60
Dates: Created 2009/01/05; Completed 2009/02/20;
PMID: 19036902, status: MEDLINE (last retrieved date: 3/9/2009)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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Associated Chemicals: Cholesterol, Dietary (0) ; DNA-Binding Proteins (0) ; Hydrocarbons, Fluorinated (0) ; RNA, Messenger (0) ; RNA, Small Interfering (0) ; Receptors, Cytoplasmic and Nuclear (0) ; Recombinant Proteins (0) ; Retinoid X Receptor alpha (0) ; Sulfonamides (0) ; TO-901317 (0) ; liver X receptor (0) ; Dexamethasone (50-02-2) ; Corticosterone (50-22-6) ; Cholesterol (57-88-5) ; Pro-Opiomelanocortin (66796-54-1) ; Adrenocorticotropic Hormone (9002-60-2)Related articles
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