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

Anna Guldvang Jensen; Cecilie Hurup Hansen; Johan J Weisser; Bent Halling-Sørensen; Bjarne Styrishave

doi:10.1016/j.reprotox.2015.10.005

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

Anna Guldvang Jensen, Cecilie Hurup Hansen, Johan J Weisser, Bent Halling-Sørensen, Bjarne Styrishave

13 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Reproductive Toxicology
Volume	58
Pages (from-to)	174-83
Number of pages	10
ISSN	0890-6238
DOIs	https://doi.org/10.1016/j.reprotox.2015.10.005
Publication status	Published - 1 Dec 2015

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@article{f145ab69085c494bac048d83849a01d9,

title = "Simvastatin decreases steroid production in the H295R cell line and decreases steroids and FSH in female rats",

abstract = "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.",

author = "Jensen, {Anna Guldvang} and Hansen, {Cecilie Hurup} and Weisser, {Johan J} and Bent Halling-S{\o}rensen and Bjarne Styrishave",

year = "2015",

month = dec,

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doi = "10.1016/j.reprotox.2015.10.005",

language = "English",

volume = "58",

pages = "174--83",

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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

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 -

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

Abstract

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