Exposure to an Extremely-Low-Frequency Magnetic Field Stimulates Adrenal Steroidogenesis via Inhibition of Phosphodiesterase Activity in a Mouse Adrenal Cell Line

PLoS One. 2016 Apr 21;11(4):e0154167. doi: 10.1371/journal.pone.0154167. eCollection 2016.

Abstract

Extremely low-frequency magnetic fields (ELF-MFs) are generated by power lines and household electrical devices. In the last several decades, some evidence has shown an association between ELF-MF exposure and depression and/or anxiety in epidemiological and animal studies. The mechanism underlying ELF-MF-induced depression is considered to involve adrenal steroidogenesis, which is triggered by ELF-MF exposure. However, how ELF-MFs stimulate adrenal steroidogenesis is controversial. In the current study, we investigated the effect of ELF-MF exposure on the mouse adrenal cortex-derived Y-1 cell line and the human adrenal cortex-derived H295R cell line to clarify whether the ELF-MF stimulates adrenal steroidogenesis directly. ELF-MF exposure was found to significantly stimulate adrenal steroidogenesis (p < 0.01-0.05) and the expression of adrenal steroid synthetic enzymes (p < 0.05) in Y-1 cells, but the effect was weak in H295R cells. Y-1 cells exposed to an ELF-MF showed significant decreases in phosphodiesterase activity (p < 0.05) and intracellular Ca2+ concentration (p < 0.01) and significant increases in intracellular cyclic adenosine monophosphate (cAMP) concentration (p < 0.001-0.05) and cAMP response element-binding protein phosphorylation (p < 0.05). The increase in cAMP was not inhibited by treatment with NF449, an inhibitor of the Gs alpha subunit of G protein. Our results suggest that ELF-MF exposure stimulates adrenal steroidogenesis via an increase in intracellular cAMP caused by the inhibition of phosphodiesterase activity in Y-1 cells. The same mechanism may trigger the increase in adrenal steroid secretion in mice observed in our previous study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex / cytology
  • Adrenal Cortex / drug effects
  • Adrenal Cortex / metabolism*
  • Aldosterone / biosynthesis
  • Aldosterone / metabolism
  • Animals
  • Benzenesulfonates / pharmacology
  • Blotting, Western
  • Calcium / metabolism
  • Cell Line
  • Corticosterone / biosynthesis
  • Corticosterone / metabolism
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Gene Expression / drug effects
  • Humans
  • Hydrocortisone / biosynthesis
  • Hydrocortisone / metabolism
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Magnetic Fields*
  • Mice
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphoric Diester Hydrolases / metabolism*
  • Phosphorylation / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Steroid 11-beta-Hydroxylase / genetics
  • Steroid 11-beta-Hydroxylase / metabolism
  • Steroids / biosynthesis*

Substances

  • 4,4,',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis(benzene-1,3-disulfonate)
  • Benzenesulfonates
  • Cyclic AMP Response Element-Binding Protein
  • Phosphoproteins
  • Steroids
  • steroidogenic acute regulatory protein
  • Aldosterone
  • Cyclic AMP
  • Steroid 11-beta-Hydroxylase
  • Phosphoric Diester Hydrolases
  • Calcium
  • Corticosterone
  • Hydrocortisone

Grants and funding

This work was supported by 25870475 JSPS (Japan Society for the Promotion of Science) KAKENHI Grant (https://www.jsps.go.jp/j-grantsinaid/).