Transcriptional changes in steroidogenesis by perfluoroalkyl acids (PFOA and PFOS) regulate the synthesis of sex hormones in H295R cells

Chemosphere. 2016 Jul:155:436-443. doi: 10.1016/j.chemosphere.2016.04.070. Epub 2016 Apr 30.

Abstract

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are two of the most widely used perfluoroalkyl acids (PFAAs). Because of their strong persistence, they have become widely distributed throughout the environment and human bodies. PFOA and PFOS are suspected to disrupt the endocrine system based upon many in vivo studies, but the underlying mechanisms are currently unclear. In this study, we investigated the endocrine-related effects of PFOA and PFOS using in vitro estrogen receptor (ER) and androgen receptor (AR) transactivation assays and steroidogenesis assay. The results showed that PFOA and PFOS exhibited weak antagonistic ER transactivation but did not exhibit agonistic ER or AR transactivation. In the steroidogenesis assay, PFOA and PFOS induced 17β-estradiol (E2) level and reduced testosterone level, which would be caused by the induction of aromatase activity. The qPCR analysis of genes involved in steroidogenesis indicates that PFOA and PFOS associate with sex hormone synthesis by the transcriptional induction of two genes, cyp19 and 3β-hsd2. Moreover, the transcriptional induction of cyp11b2 by PFOS suggests that this chemical may underlie the disruption of several physiological functions related to aldosterone. The results of the current study suggest that PFOA and PFOS are potential endocrine disrupting chemicals (EDCs) and provide information for further studies on the molecular events that initiate the adverse endocrine effects.

Keywords: Aromatase; ER/AR transactivation; Endocrine disruptor chemical; Perfluorooctane sulfonate; Perfluorooctanoic acid; Steroidogenesis.

MeSH terms

  • Adrenocortical Carcinoma / genetics*
  • Adrenocortical Carcinoma / metabolism
  • Adrenocortical Carcinoma / pathology
  • Alkanesulfonic Acids / pharmacology*
  • Aromatase / genetics
  • Aromatase / metabolism
  • Biological Assay
  • Caprylates / pharmacology*
  • Endocrine Disruptors / pharmacology*
  • Endocrine System / drug effects*
  • Estrogens / pharmacology
  • Fluorocarbons / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gonadal Steroid Hormones / metabolism*
  • Humans
  • Real-Time Polymerase Chain Reaction
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Receptors, Estrogen / genetics*
  • Receptors, Estrogen / metabolism
  • Tumor Cells, Cultured

Substances

  • Alkanesulfonic Acids
  • Caprylates
  • Endocrine Disruptors
  • Estrogens
  • Fluorocarbons
  • Gonadal Steroid Hormones
  • Receptors, Androgen
  • Receptors, Estrogen
  • perfluorooctanoic acid
  • perfluorooctane sulfonic acid
  • Aromatase
  • CYP19A1 protein, human