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 language | English |
---|---|
Pages (from-to) | 69-75 |
Number of pages | 7 |
Journal | Molecular and Cellular Endocrinology |
Volume | 362 |
Issue number | 1-2 |
DOIs | |
Publication status | Published - 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