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

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

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.

MeSH terms

  • Adrenal Cortex / drug effects*
  • Adrenal Cortex / metabolism
  • Animals
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / toxicity*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fertility / drug effects
  • Follicle Stimulating Hormone / biosynthesis*
  • Follicle Stimulating Hormone / blood
  • Gas Chromatography-Mass Spectrometry
  • Gonadal Steroid Hormones / biosynthesis*
  • Gonadal Steroid Hormones / blood
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / toxicity*
  • Luteinizing Hormone / biosynthesis
  • Luteinizing Hormone / blood
  • Rats, Sprague-Dawley
  • Reproduction / drug effects
  • Risk Assessment
  • Simvastatin / toxicity*
  • Tandem Mass Spectrometry
  • Time Factors

Substances

  • Endocrine Disruptors
  • Gonadal Steroid Hormones
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Simvastatin