Cis-bifenthrin inhibits cortisol and aldosterone biosynthesis in human adrenocortical H295R cells via cAMP signaling cascade

Environ Toxicol Pharmacol. 2022 Jan:89:103784. doi: 10.1016/j.etap.2021.103784. Epub 2021 Dec 9.

Abstract

Cis-bifenthrin (cis-BF) is a common-used pyrethroid insecticide frequently detected in environmental and biological matrices. Mounting evidence highlights the endocrine disrupting effects of cis-BF due to anti-estrogenic or anti-androgenic activity. However, little is known about the exposure effects of cis-BF on adrenal cortex function. In this study, effects of cis-BF on biosynthesis of adrenal steroids, as well as the potential mechanisms were investigated in human adrenocortical carcinoma (H295R) cells. Cis-BF decreased basal production levels of cortisol and aldosterone, as well as cAMP-induced production of cortisol. Both he basal and cAMP-stimulated transcriptional levels of several steroidogenic genes were significantly down-regulated by cis-BF. As an important rate-limiting enzyme in steroidogenesis, the protein level of StAR was prohibited by cis-BF on both basal and cAMP-induced conditions. Intracellular level of cAMP was significantly reduced by cis-BF. Overall, these data suggest that cis-BF may inhibit the biosynthesis of cortisol and aldosterone via disrupting cAMP signaling cascade.

Keywords: Cis-bifenthrin; Cyclic adenosine monophosphate; H295R cells; Pyrethroid insecticides; Steroidogenic genes.

MeSH terms

  • Adrenal Cortex / drug effects*
  • Aldosterone / biosynthesis
  • Cell Line, Tumor
  • Cyclic AMP / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydrocortisone / biosynthesis
  • Insecticides / toxicity*
  • Pyrethrins / toxicity*

Substances

  • Insecticides
  • Pyrethrins
  • Aldosterone
  • bifenthrin
  • Cyclic AMP
  • Hydrocortisone