Beta-endorphin and adrenocorticotropin release from rat adenohypophysis in vitro: evidence for local modulation by arachidonic acid metabolites of the cyclooxygenase and lipoxygenase pathway.
This study was performed to examine an involvement of adenohypophysial arachidonic acid metabolites in the local mechanisms controlling the release of peptide hormones from the corticotrope cells of the anterior pituitary gland. Therefore, we investigated the effect of blockers of the lipoxygenase (nordihydroguaiaretic acid, NDGA), cyclooxygenase (indomethacin) or both of these enzyme systems (BW755C; eicosatetraynoic acid, ETYA) on the release of beta-endorphin-like (beta-E-IR) and adrenocorticotropin-like immunoreactivity (ACTH-IR) from rat anterior pituitary quarters incubated in vitro. NDGA and ETYA did not influence the basal release of beta-E- and ACTH-IR. However, upon stimulation by arginine-vasopressin (AVP) or synthetic ovine corticotropin-releasing factor (CRF(1-41], NDGA inhibited beta-E-IR release by 40%. ETYA inhibited AVP-induced release of beta-E- and ACTH-IR by 75%. Indomethacin and BW755C (lower concentration) enhanced beta-E-IR release, induced by AVP, by about 100%, whereas BW755C (higher concentration) had no effect. When indomethacin was present, NDGA, ETYA and BW755C (higher concentration) inhibited AVP-induced release of beta-E- and ACTH-IR. Prostaglandin E2 (PGE2) inhibited beta-E-IR release in response to AVP but failed to do so in the presence of NDGA. 12-OH-5,8,10,14-eicosatetraenoic acid (12-HETE) had no effect. When anterior pituitary quarters were incubated with 3H-arachidonic acid (3H-AA), NDGA and BW755C (higher concentration) but not indomethacin and BW755C (lower concentration) blocked the formation of a metabolite which co-migrated with 12-HETE on thin-layer chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000502:physiology*; D002396:Catechols / Q000494:pharmacology; D015232:Dinoprostone; D004723:Endorphins / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009637:Masoprocol; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin
D001095:Arachidonic Acids; D002396:Catechols; D004723:Endorphins; D011458:Prostaglandins E; D011720:Pyrazoles; D015117:5,8,11,14-Eicosatetraynoic Acid; D001615:beta-Endorphin; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; C029510:4,7,10,13-eicosatetraynoic acid; D009637:Masoprocol; D000324:Adrenocorticotropic Hormone; D015232:Dinoprostone; D007213:Indomethacin