Simvastatin decreases steroid production in the H295R cell line and decreases steroids and FSH in female rats

TY - JOUR

T1 - Simvastatin decreases steroid production in the H295R cell line and decreases steroids and FSH in female rats

AU - Jensen, Anna Guldvang

AU - Hansen, Cecilie Hurup

AU - Weisser, Johan J

AU - Halling-Sørensen, Bent

AU - Styrishave, Bjarne

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Endocrine modulating effects of Simvastatin (SV) and its metabolite, Simvastatin β-hydroxy acid (SVA), were investigated in H295R cells and in female Sprague-Dawley (SPRD) rats. H295R cells were exposed to SV and SVA concentrations from 0 to 10 μM for 48 h Four groups of SPRD rats received 0 (CT), 1.3 (L), 5.0 (M), and 20.0 (H). mg SV/kg bw/day for 14 days. 10 Steroids were investigated in H295R growth media, and in tissues and plasma from rats using GC-MS/MS. Plasma LH and FSH were quantified by ELISA. In the H295R assay, SV and SVA particularly decreased progestagens with IC50-values from 0.10-0.13. μM for SV and from 0.019-0.055. μM for SVA. In rats, SV decreased progestagens in ovaries, brain and plasma, and plasma FSH in the M (72.4% decrease) and H group (76.6% decrease). Because progestagens and gonadotropins are major players in fertility, administration of SV might exert negative effects on female reproduction.

AB - Endocrine modulating effects of Simvastatin (SV) and its metabolite, Simvastatin β-hydroxy acid (SVA), were investigated in H295R cells and in female Sprague-Dawley (SPRD) rats. H295R cells were exposed to SV and SVA concentrations from 0 to 10 μM for 48 h Four groups of SPRD rats received 0 (CT), 1.3 (L), 5.0 (M), and 20.0 (H). mg SV/kg bw/day for 14 days. 10 Steroids were investigated in H295R growth media, and in tissues and plasma from rats using GC-MS/MS. Plasma LH and FSH were quantified by ELISA. In the H295R assay, SV and SVA particularly decreased progestagens with IC50-values from 0.10-0.13. μM for SV and from 0.019-0.055. μM for SVA. In rats, SV decreased progestagens in ovaries, brain and plasma, and plasma FSH in the M (72.4% decrease) and H group (76.6% decrease). Because progestagens and gonadotropins are major players in fertility, administration of SV might exert negative effects on female reproduction.

U2 - 10.1016/j.reprotox.2015.10.005

DO - 10.1016/j.reprotox.2015.10.005

M3 - Journal article

C2 - 26476359

SN - 0890-6238

VL - 58

SP - 174

EP - 183

JO - Reproductive Toxicology

JF - Reproductive Toxicology

ER -