Evaluation of signal transduction pathways mediating the nuclear exclusion of the androgen receptor by melatonin

Z. Lupowitz, A. Rimler, N. Zisapel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The intracellular signaling pathways mediating the nuclear exclusion of the androgen receptor (AR) by melatonin were evaluated in PC3 cells stably transfected with the AR. The melatonin-induced nuclear exclusion of the AR by melatonin (100 nM, 3 h) was blocked by LY 83583 (an inhibitor of guanylyl cyclases). 8-Bromo-cGMP (a cell-permeable cGMP analog), mimicked the effect of melatonin, as did ionomycin (a calcium ionophore) and PMA [an activator of protein kinase C (PKC)], and their effects were blocked by GF-109203X (a selective PKC inhibitor). BAPTA (an intracellular calcium chelator) blocked the effects of melatonin and 8-bromo-cGMP but not of PMA. inhibition or activation of the protein kinase A pathway did not affect basal or melatonin-mediated AR localization. We conclude that the melatonin-mediated rise in cGMP elicits AR nuclear exclusion via a pathway involving increased intracellular calcium and PKC activation. These results define a novel signaling pathway that regulates AR localization and androgen responses in target cells.

Original languageEnglish
Pages (from-to)2129-2135
Number of pages7
JournalCellular and Molecular Life Sciences
Volume58
Issue number14
DOIs
StatePublished - 2001

Keywords

  • Androgen receptor
  • CGMP
  • Melatonin
  • Nuclear localization
  • Protein kinase A
  • Protein kinase C
  • Protein kinase G

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