Arachidonic acid metabolism and thyrotropin secretion in vitro.
We investigated the role of arachidonic acid and certain of its metabolic products in the control of thyrotropin (TSH) secretion in vitro. Phospholipase A2 and 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), which increase the intracellular availability of arachidonic acid, potently stimulated TSH release from anterior pituitary cells continuously perifused in columns and from hemipituitary glands in vitro. The effect was dose-dependent and reversible. Conversely, quinacrine (50 microM), an inhibitor of phospholipase A2 activity, inhibited basal and stimulated TSH release from pituitary cells perifused in columns. Exogenous arachidonic acid (1-100 microM) did not produce any significant effect on TSH release from hemipituitary glands in vitro. Nordihydroguaiaretic acid (NDGA), a specific inhibitor of the lipoxygenase pathway, dose-dependently inhibited basal TSH release from anterior pituitary glands incubated in vitro. Moreover, 50 microM NDGA antagonized the stimulatory effect of thyrotropin releasing hormone (TRH), phospholipase A2 and PMA on TSH release. BW755c, another lipoxygenase inhibitor, also inhibited TRH-stimulated TSH secretion. In contrast, 10-100 microM indomethacin, a potent blocker of the cyclooxygenase pathway, did not significantly modify either basal or TRH-stimulated TSH secretion from hemipituitary glands in vitro. These data suggest that arachidonic acid metabolism is involved in TSH secretion in vitro, although incubation of pituitary glands with the fatty acid did not apparently modify in our conditions basal TSH secretion. The eventual effect of arachidonate appears to be at least partially due to the action of its lipoxygenase pathway products.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D010902:Pituitary Gland / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D001095:Arachidonic Acids; D002396:Catechols; D011720:Pyrazoles; D016718:Arachidonic Acid; D013973:Thyrotropin-Releasing Hormone; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D013972:Thyrotropin; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin