The
GnRH receptor (GnRHR) mediates the pituitary functions of
GnRH, as well as its anti-proliferative effects in
sex hormone-dependent
cancer cells. Here we compare the signaling of GnRHR in pituitary gonadotrope cell lines vs.
prostate cancer cell lines. We first noticed that the expression level of PKCα, PKCβII and PKCε is much higher in αT3-1 and LβT2 gonadotrope cell lines vs. LNCaP and DU-145 cell lines, while the opposite is seen for PKCδ. Activation of PKCα, PKCβII and PKCε by
GnRH is relatively transient in αT3-1 and LβT2 gonadotrope cell lines and more prolonged in LNCaP and DU-145 cell lines. On the otherhand, the activation and re-distribution of the above
PKCs by PMA was similar for both gonadotrope cell lines and
prostate cancer cell lines. Activation of ERK1/2 by
GnRH and PMA was robust in the gonadotrope cell lines, with a smaller effect observed in the
prostate cancer cell lines. The Ca(2+)
ionophore A23187 stimulated ERK1/2 in gonadotrope cell lines but not in
prostate cancer cell lines.
GnRH, PMA and
A23187 stimulated JNK activity in gonadotrope cell lines, with a more sustained effect in
prostate cancer cell lines. Sustained activation of p38 was observed for PMA and
A23187 in Du-145 cells, while p38 activation by
GnRH, PMA and
A23187 in LβT2 cells was transient. Thus, differential expression and re-distribution of
PKCs by
GnRH and the transient vs. the more sustained nature of the activation of the PKC-MAPK cascade by
GnRH in gonadotrope cell lines vs.
prostate cancer cell lines respectively, may provide the mechanistic basis for the cell context-dependent differential
biological responses observed in
GnRH interaction with pituitary gonadotropes vs.
prostate cancer cells.