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.
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Received 31 July 2001; received after revision 18 September 2001; accepted 30 October 2001
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Lupowitz, Z., Rimler, A. & Zisapel, N. Evaluation of signal transduction pathways mediating the nuclear exclusion of the androgen receptor by melatonin. CMLS, Cell. Mol. Life Sci. 58, 2129–2135 (2001). https://doi.org/10.1007/PL00000842
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DOI: https://doi.org/10.1007/PL00000842