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 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.
authors.affiliation: Toxicology Laboratory, Department of Pharmacy, Section of Analytical Biosciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen OE, Denmark. Electronic address: anna_guldvang@hotmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Guldvang
authors.affiliation: Toxicology Laboratory, Department of Pharmacy, Section of Analytical Biosciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen OE, Denmark.
authors.forename: Cecilie Hurup
authors.initials: CH
authors.lastname: Hansen
authors.affiliation: Toxicology Laboratory, Department of Pharmacy, Section of Analytical Biosciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen OE, Denmark.
authors.forename: Johan J
authors.initials: JJ
authors.lastname: Weisser
authors.affiliation: Toxicology Laboratory, Department of Pharmacy, Section of Analytical Biosciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen OE, Denmark.
authors.forename: Bent
authors.initials: B
authors.lastname: Halling-Sørensen
authors.affiliation: Toxicology Laboratory, Department of Pharmacy, Section of Analytical Biosciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen OE, Denmark.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Styrishave
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005298:Fertility / Q000187:drug effects; D005640:Follicle Stimulating Hormone / Q000096:biosynthesis* / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis* / Q000097:blood; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000633:toxicity*; D007986:Luteinizing Hormone / Q000096:biosynthesis / Q000097:blood; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D018570:Risk Assessment; D019821:Simvastatin / Q000633:toxicity*; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D052244:Endocrine Disruptors; D012739:Gonadal Steroid Hormones; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D019821:Simvastatin
keywords: Female Sprague-Dawley rats; H295R cells; HPG axis; Simvastatin; Statin; Steroidogenesis