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Reprod Toxicol. 2015 Dec;58:174-83. doi: 10.1016/j.reprotox.2015.10.005. Epub 2015 Oct 23.

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

Author information

1
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.
2
Toxicology Laboratory, Department of Pharmacy, Section of Analytical Biosciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen OE, Denmark.

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.

KEYWORDS:

Female Sprague-Dawley rats; H295R cells; HPG axis; Simvastatin; Statin; Steroidogenesis

PMID:
26476359
DOI:
10.1016/j.reprotox.2015.10.005
[Indexed for MEDLINE]

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