FXR agonist GW4064 increases plasma glucocorticoid levels in C57BL/6 mice

Menno Hoekstra*, Ronald J. van der Sluis, Zhaosha Li, Maaike H. Oosterveer, Albert K. Groen, Theo J. C. Van Berkel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)

Abstract

Since high expression of farnesoid X receptor (FXR) has been detected in glucocorticoid-producing adrenocortical cells, we evaluated the potential role of FXR in adrenal glucocorticoid production.

FXR agonist GW4064 increased fasting plasma corticosterone levels (+45%; P <0.01) in C57BL/6 mice, indicative of enhanced adrenal steroidogenesis. GW4064 treatment did not affect plasma ACTH levels, adrenal weight, or adrenal expression of steroidogenic genes. Scavenger receptor BI (SR-BI) mRNA and protein expression, respectively, increased 1.9-fold (P <0.01) and 1.5-fold, which suggests a stimulated lipoprotein-associated cholesterol uptake into the adrenals upon GW4064 treatment. In line with an enhanced flux of cellular cholesterol into the steroidogenic pathway, adrenal unesterified and esterified cholesterol stores were 21-41% decreased (P <0.01) upon GW4064 treatment.

In conclusion, we have shown that the FXR agonist GW4064 stimulates plasma corticosterone levels in C57BL/6 mice. Our findings suggest a novel role for FXR in the modulation of adrenal cholesterol metabolism and glucocorticoid synthesis in mice. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume362
Issue number1-2
DOIs
Publication statusPublished - 15-Oct-2012

Keywords

  • Glucocorticoid
  • Corticosterone
  • Cholesterol
  • FXR
  • GW4064
  • SR-BI
  • FARNESOID-X-RECEPTOR
  • ACID-BINDING-PROTEIN
  • GENE-EXPRESSION
  • PROMOTER
  • TARGET
  • RAT
  • ACTIVATION
  • DEFICIENT
  • REVEALS
  • ABSENCE

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