Differential involvement of phospholipase A2 in phorbol ester-induced luteinizing hormone and growth hormone release from rat anterior pituitary tissue.

The protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu) induced the release of both luteinizing hormone (LH) and growth hormone (GH) from proestrous rat anterior pituitary pieces in vitro. Phorbol 12,13-dibutyrate-induced LH, but not GH release was readily inhibited by the phospholipase A2 (PLA2) inhibitors, quinacrine, aristolochic acid, ONO-RS-082 and chloracysine. Furthermore, PDBu induced release of [3H]arachidonic acid ([3H]AA) from pre-labelled anterior pituitary tissue that was prevented in the presence of quinacrine, aristolochic acid and ONO-RS-082 but not the diglyceride lipase inhibitor RHC 80267. The effect of PDBu was completely inhibited by staurosporine and the selective PKC inhibitor Ro 31-8220 but only partially by low concentrations of H7; consistent with the involvement of both H7-sensitive and H7-resistant forms of PKC in the activation of PLA2 by PDBu. The protein synthesis inhibitor cycloheximide inhibited the release of both [3H]AA and LH that had been induced by PDBu, whereas LH release induced by the PLA2 activator mellitin was cycloheximide-insensitive. These results suggest that PKC activators may induce LH but not GH release from anterior pituitary tissue by a mechanism involving activation of a PLA2, brought about by a process which is reliant on protein synthesis.