Testosterone-induced modulation of peroxisomal morphology and peroxisome-related gene expression in brown trout (Salmo trutta f. fario) primary hepatocytes

Aquat Toxicol. 2017 Dec:193:30-39. doi: 10.1016/j.aquatox.2017.09.026. Epub 2017 Sep 28.

Abstract

Disruption of androgenic signaling has been linked to possible cross-modulation with other hormone-mediated pathways. Therefore, our objective was to explore effects caused by testosterone - T (1, 10 and 50μM) in peroxisomal signaling of brown trout hepatocytes. To study the underlying paths involved, several co-exposure conditions were tested, with flutamide - F (anti-androgen) and ICI 182,780 - ICI (anti-estrogen). Molecular and morphological approaches were both evaluated. Peroxisome proliferator-activated receptor alpha (PPARα), catalase and urate oxidase were the selected targets for gene expression analysis. The vitellogenin A gene was also included as a biomarker of estrogenicity. Peroxisome relative volumes were estimated by immunofluorescence, and transmission electron microscopy was used for qualitative morphological control. The single exposures of T caused a significant down-regulation of urate oxidase (10 and 50μM) and a general up-regulation of vitellogenin. A significant reduction of peroxisome relative volumes and smaller peroxisome profiles were observed at 50μM. Co-administration of T and ICI reversed the morphological modifications and vitellogenin levels. The simultaneous exposure of T and F caused a significant and concentration-dependent diminishing in vitellogenin expression. Together, the findings suggest that in the tested model, T acted via both androgen and estrogen receptors to shape the peroxisomal related targets.

Keywords: Fish; Flutamide; Hepatocytes; ICI 182,780; Peroxisomes; Testosterone.

MeSH terms

  • Androgen Antagonists / pharmacology
  • Animals
  • Catalase / genetics
  • Catalase / metabolism
  • Down-Regulation
  • Endocrine Disruptors / toxicity*
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology
  • Flutamide / pharmacology
  • Fulvestrant
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Hepatocytes / ultrastructure
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Peroxisomes / drug effects*
  • Peroxisomes / metabolism
  • Peroxisomes / ultrastructure
  • Signal Transduction / drug effects
  • Testosterone / toxicity*
  • Trout / genetics
  • Trout / physiology*
  • Up-Regulation
  • Urate Oxidase / genetics
  • Urate Oxidase / metabolism
  • Vitellogenins / genetics
  • Vitellogenins / metabolism
  • Water Pollutants, Chemical / toxicity*

Substances

  • Androgen Antagonists
  • Endocrine Disruptors
  • Estrogen Antagonists
  • PPAR alpha
  • Vitellogenins
  • Water Pollutants, Chemical
  • Fulvestrant
  • Testosterone
  • Estradiol
  • Flutamide
  • Catalase
  • Urate Oxidase