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

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.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Hoekstra M,van der Sluis RJ,Li Z,Oosterveer MH,Groen AK,Van Berkel TJ

doi

10.1016/j.mce.2012.05.010

subject

Has Abstract

pub_date

2012-10-15 00:00:00

pages

69-75

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(12)00304-8

journal_volume

362

pub_type

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