RHC 80267 inhibits thyrotropin-stimulated prostaglandin release from rat thyroid lobes

In the present report, we studied the effect of the diglyceride (DG) lipase inhibitor, RHC 80267 on basal and thyrotropin (TSH)-stimulated prostaglandin (PG) release from rat thyroid lobes Further, we tested the effect of RHC 80267 on phosphatidylinositol phospholipase C (PIPLC), DG lipase, and arachidonate cyclo-oxygenase activities in rat thyroid cytosol, plasma membrane, and whole homogenate preparations, respectively. Whereas RHC 80267 inhibited DG lipase activity in a dose-related manner from 0.5-10 microns (17-80% inhibition), it failed to inhibit either PIPLC or arachidonate cyclo-oxygenase activities by more than 9% when tested at 5 and 10 microns (n = 3). RHC 80267 reduced TSH-stimulated 6-keto-PGF1alpha and PGF2alpha release by 100 +/- 14% and 57 +/- 12%, respectively (means + S.E.; p less than 0.01 for both; n = 10-12); the diglyceride lipase inhibitor did not reduce basal release of either PG. These data provide additional evidence which implicate a PIPLC-DG lipase pathway in TSH-stimulated PG synthesis in thyroid.