Lipoxygenase products of arachidonic acid stimulate LHRH release from rat median eminence.
Exogenous arachidonic acid (AA) incubated in presence of male rat hypothalamus, shows a low rate of conversion (less than 1%) of the substrate with a major product, identified as 12-hydroxyeicosatetraenoic acid (12-HETE) by reverse phase-high performance liquid chromatography (rpHPLC) and gas chromatography-mass spectrometry (GC-MS). Furthermore, immunoreactive 12-HETE estimated after purification on rpHPLC is produced by hypothalamus slices or median eminences (MEs) incubated in absence of any exogenous precursor. The effect of 12-HETE was tested on the release of LHRH from rat MEs after a 30-min incubation and was compared to the effect of another lipoxygenase product, 5-HETE, and to the well-known stimulatory effect of prostaglandin E2 (PGE2). The three AA metabolites stimulate LHRH release. A significant stimulatory effect on LHRH release is obtained with 10(-9) M of 12-HETE and only with 10(-8) M of 5-HETE or PGE2. Furthermore, the effect of higher concentrations is different according to the eicosanoid tested. The maximal response (176% of the control) is reached with 12-HETE at 10(-8) M. No significant change is observed at 10(-7) and 10(-6) M. The response with 5-HETE is also maximal (162% of the control) at 10(-8) M but decreases significantly (only 117% of the control) at 10(-6) M. The amplitude of the response to PGE2 is larger and higher, reaching a plateau (300% of the control) at 10(-6) M. 12-HETE has no effect on somatostatin (SRIF), release, as already known for PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D015232:Dinoprostone; D004537:Eicosanoic Acids / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism*; D066298:In Vitro Techniques; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats
C025347:5-hydroxyarachidic acid; D001095:Arachidonic Acids; D004537:Eicosanoic Acids; D006893:Hydroxyeicosatetraenoic Acids; D011458:Prostaglandins E; D016718:Arachidonic Acid; D007987:Gonadotropin-Releasing Hormone; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D008084:Lipoxygenase; D015232:Dinoprostone