Staurosporine enhances gonadotrophin-releasing hormone-stimulated luteinizing hormone secretion.
In intact sheep gonadotropes, the protein kinase inhibitor, staurosporine, inhibited the stimulatory effect of phorbol 12-myristate 13-acetate (PMA) on luteinizing hormone (LH) secretion. Under the same conditions staurosporine enhanced gonadotrophin-releasing hormone (GnRH)-stimulated LH exocytosis without altering the EC50 of GnRH and without affecting basal LH exocytosis. These results suggest that PKC does not play a major role in mediating acute GnRH-stimulated LH exocytosis. Furthermore, they demonstrate that staurosporine enhances GnRH stimulus-secretion coupling. Both extracellular Ca2(+)-dependent and Ca2(+)-independent components of GnRH-stimulated LH secretion were enhanced by the drug. Staurosporine had no effect on GnRH stimulation of cAMP and inositol phosphate synthesis. In permeabilized cells staurosporine did not enhance Ca2(+)- and cAMP-stimulated LH exocytosis. Based on these results we hypothesize that staurosporine inhibits a protein kinase which is activated by GnRH and which negatively modulates GnRH stimulus-secretion coupling.
van der Merwe
P A
PA
Department of Chemical Pathology, University of Cape Town Medical School, Observatory, South Africa.
Millar
R P
RP
Wakefield
I K
IK
Macrae
M B
MB
Davidson
J S
JS
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D007295:Inositol Phosphates / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D010906:Pituitary Hormone-Releasing Hormones / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D012756:Sheep; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D007295:Inositol Phosphates; D010906:Pituitary Hormone-Releasing Hormones; D047428:Protein Kinase Inhibitors; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate