Steroid hormone related effects of marine persistent organic pollutants in human H295R adrenocortical carcinoma cells

Toxicol In Vitro. 2015 Jun;29(4):769-78. doi: 10.1016/j.tiv.2015.03.002. Epub 2015 Mar 9.

Abstract

Persistent organic pollutants (POPs) such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorobiphenyl (PCB) 126 and 153, perfluorooctanesulfonic acid (PFOS), hexabromocyclododecane (HBCD), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), tributyltin (TBT), and methylmercury (MeHg) can be accumulated in seafood and then form a main source for human exposure. Some POPs have been associated with changes in steroid hormone levels in both humans and animals. This study describes the in vitro effects of these POPs and mixtures thereof in H295R adrenocortical carcinoma cells. Relative responses for 13 steroid hormones and 7 genes involved in the steroidogenic pathway, and CYP1A1, were analyzed. PFOS induced the most pronounced effects on steroid hormone levels by significantly affecting 9 out of 13 hormone levels measured, with the largest increases found for 17β-estradiol, corticosterone, and cortisol. Furthermore, TCDD, both PCBs, and TBT significantly altered steroidogenesis. Increased steroid hormone levels were accompanied by related increased gene expression levels. The differently expressed genes were MC2R, CYP11B1, CYP11B2, and CYP19A1 and changes in gene expression levels were more sensitive than changes in hormone levels. The POP mixtures tested showed mostly additive effects, especially for DHEA and 17β-estradiol levels. This study shows that some seafood POPs are capable of altering steroidogenesis in H295R cells at concentrations that mixtures might reach in human blood, suggesting that adverse health effects cannot be excluded.

Keywords: Adrenal cortex cell line; Endocrine disruption; Gene expression; H295R; Persistent organic pollutants (POPs); Steroid hormones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA, Complementary / biosynthesis
  • Endocrine Disruptors / toxicity*
  • Gene Expression Regulation / drug effects
  • Hormones / metabolism*
  • Humans
  • RNA / biosynthesis
  • RNA / isolation & purification
  • Steroids / metabolism*
  • Water Pollutants, Chemical / toxicity*

Substances

  • DNA, Complementary
  • Endocrine Disruptors
  • Hormones
  • Steroids
  • Water Pollutants, Chemical
  • RNA