The ability of GnRH to modulate protein kinase- C (PKC) activity was examined in perifused rat pituitary cell cultures. Under these conditions, LH release and GnRH receptor number remained unchanged after repeated pulses of 1 nM GnRM, whereas PKC (measured both enzymatically and by radioligand assay) showed an initial increase in kinase activity after the first pulse of GnRH (-2-fold), followed by downregulation of PKC activity with subsequent pulses of the releasing hormone. It was also observed that the GnRH-stimulated down-regulation of PKC was dependent on the presence of extracellular calcium, which was not the case for the initial upregulation of PKC. These findings are consistent with a modulating role of the GnRH receptor on PKC activity through a Ca2+-dependent process. This study also provides further evidence that GnRH-stimulated LH release and PKC activity can be uncoupled. (Endocrinology127: 2393–2399, 1990)

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