Simvastatin treatment aggravates the glucocorticoid insufficiency associated with hypocholesterolemia in mice

Abstract Background and aims Statin treatment disrupts HMG-CoA reductase-mediated endogenous cholesterol synthesis and lowers plasma LDL-cholesterol levels. Although statin treatment can theoretically impair adrenal steroid hormone synthesis, thus far, no effect on glucocorticoid output has been des...

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Bibliographic Details
Published in:Atherosclerosis 2017-06, Vol.261, p.99-104
Main Authors: Ouweneel, Amber B, van der Sluis, Ronald J, Nahon, Joya E, Van Eck, Miranda, Hoekstra, Menno
Format: Article
Language:English
Subjects:
Adrenal
Adrenal Cortex Function Tests
Adrenal Glands - drug effects
Adrenal Glands - metabolism
Adrenal Glands - physiopathology
Adrenal Insufficiency - blood
Adrenal Insufficiency - chemically induced
Adrenal Insufficiency - physiopathology
Adrenocorticotropic Hormone - administration & dosage
Animals
Apolipoprotein A-I - deficiency
Apolipoprotein A-I - genetics
Biomarkers - blood
Cardiovascular
Cholesterol - blood
Cholesterol synthesis
Corticosterone - blood
Corticosterone - deficiency
Disease Models, Animal
Gene Expression Regulation
Glucocorticoid
Hydroxymethylglutaryl-CoA Reductase Inhibitors - toxicity
Hypercholesterolemia - blood
Hypercholesterolemia - drug therapy
Hypercholesterolemia - genetics
Hypercholesterolemia - physiopathology
Liver - drug effects
Liver - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, LDL - deficiency
Receptors, LDL - genetics
Simvastatin
Simvastatin - toxicity
Steroidogenesis
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Summary:Abstract Background and aims Statin treatment disrupts HMG-CoA reductase-mediated endogenous cholesterol synthesis and lowers plasma LDL-cholesterol levels. Although statin treatment can theoretically impair adrenal steroid hormone synthesis, thus far, no effect on glucocorticoid output has been described, as LDL-cholesterol levels usually remain within the physiological range. However, novel statin-based treatment regimens that dramatically decrease LDL-cholesterol levels are currently employed. Here, we assessed whether inhibition of cholesterol synthesis under these relatively hypocholesterolemic conditions may alter adrenal glucocorticoid output. Methods Hypocholesterolemic apolipoprotein A1 ( apoA1 ) knockout mice were administered high dose simvastatin twice daily for 3 days. Results Simvastatin treatment did not change plasma cholesterol levels or modify the adrenal expression levels of genes involved in cholesterol metabolism. However, simvastatin treatment lowered basal plasma levels of the primary glucocorticoid corticosterone (−62%; p  
ISSN:0021-9150
1879-1484
DOI:10.1016/j.atherosclerosis.2017.02.014