Atorvastatin decreases steroid production in H295R cells and in major endocrine tissues of male rats.

Atorvastatin decreases steroid production in H295R cells and in major endocrine tissues of male rats. Arch Toxicol. 2018 Mar 24;: Authors: Munkboel CH, Baake MLK, Styrishave B Abstract Obesity is increasing worldwide, and since obesity is associated with dyslipidemia, the consumption of cholesterol-lowering pharmaceuticals has increased. The aim of this study was therefore to study potential endocrine disrupting effects of one of the world's most frequently prescribed drugs, the cholesterol-lowering drug, atorvastatin (ATO) in vitro using the H295R steroidogenesis assay and in vivo using male Sprague-Dawley rats. We analyzed all major steroids in the mammalian steroidogenesis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In vitro, ATO significantly decreased all steroids in the H295R steroidogenesis at concentrations close to human plasma Cmax values, with an IC50 value for testosterone of 0.093 ± 0.033 µM. Additionally, we determined steroid hormone levels in testis, adrenals, brain and plasma from rats after 14 days of exposure to three therapeutically relevant doses of ATO and observed pronounced decreasing steroid levels in particular in testis and adrenals but also in brain and plasma. In testis, all major steroidogenic enzymes were up-regulated, indicating autocrine and/or paracrine compensation for the decrease in steroid production by this tissue. In adrenals, StAR and CYP11A1 gene expression were d...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research