Staurosporine enhances gonadotrophin-releasing hormone-stimulated luteinizing hormone secretion |
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Authors: | P A van der Merwe R P Millar I K Wakefield M B Macrae J S Davidson |
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Affiliation: | Department of Chemical Pathology, University of Cape Town Medical School, Observatory, South Africa. |
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Abstract: | 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. |
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