Interleukin-6 increases adrenal androgen release by regulating the expression of steroidogenic proteins in NCI-H295R cells

J Cell Physiol. 2020 Dec;235(12):9432-9444. doi: 10.1002/jcp.29748. Epub 2020 Apr 28.

Abstract

The purpose of this study was to investigate the potential mechanism of interleukin-6 (IL-6) on the stimulation of excessive androgen secretion in human NCI-H295R adrenocortical cells. We performed transcriptome sequencing of cancer and paracancerous tissues obtained from functional adrenal cortical adenomas. The secretion of dehydroepiandrosterone sulfate (DHEAS) in NCI-H295R cells was detected by a chemiluminescence assay. The expression of messenger RNA (mRNA) was detected by real-time polymerase chain reaction and that of protein was detected by western blotting. The expression of secretogranin II (SCG2) and IL-6 were significantly increased in cancer tissues. Upregulation of mRNA and protein levels of AKR1C3, CYP11A, CYP17A1, 3βHSD, and SULT2A1 was observed after stimulation with IL-6. IL-6 could also increase the expression of StAR mRNA and proteins. Our results suggest that IL-6 can promote androgen secretion by regulating the expression of genes related to androgen pathways.

Keywords: NCI-H295R; androgen; functional adrenal cortical adenomas; interleukin-6; transcriptome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex / drug effects*
  • Adrenal Cortex / metabolism
  • Androgens / metabolism*
  • Blotting, Western / methods
  • Cell Line, Tumor
  • Humans
  • Hydrocortisone / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology*
  • RNA, Messenger / genetics
  • Transcriptional Activation / drug effects*

Substances

  • Androgens
  • Interleukin-6
  • RNA, Messenger
  • Hydrocortisone