Simvastatin decreases steroid production in the H295R cell line and decreases steroids and FSH in female rats
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Simvastatin decreases steroid production in the H295R cell line and decreases steroids and FSH in female rats. / Jensen, Anna Guldvang; Hansen, Cecilie Hurup; Weisser, Johan J; Halling-Sørensen, Bent; Styrishave, Bjarne.
In: Reproductive Toxicology, Vol. 58, 12.2015, p. 174-83.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2015/12
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 10μM for 48h. 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 0.10-0.13μM for SV and from 0.019-0.055μM 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 10μM for 48h. 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 0.10-0.13μM for SV and from 0.019-0.055μM 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
VL - 58
SP - 174
EP - 183
JO - Reproductive Toxicology
JF - Reproductive Toxicology
SN - 0890-6238
ER -
ID: 161588544