Staurosporine enhances gonadotrophin‐releasing hormone‐stimulated luteinizing hormone secretion

FEBS Letters

Wakeneld, Ian K.¹  Macrae, M.Bruce¹  van der Merwe, P.Anton¹  Millar, Robert P.¹  Davidson, James S.¹ 

[1] Department of Chemical Pathology, University of Cape Town Medical School, Observatory 7925, South Africa

关键词: Luteinizing hormone;    Gonadotropin-releasing hormone;    Staurosporine;    Protein kinase C;    Gonadotrope;   

DOI  :  10.1016/0014-5793(90)80301-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown