Mechanism of action of gonadotropin releasing hormone: Role of lipoxygenase products of arachidonic acid in luteinizing hormone release

Zvi Naor, Ludwig Kiesel, Jack Y. Vanderhoek, Kevin J. Catt

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanism of action of gonadotropin-releasing hormone (GnRH) upon pituitary luteinizing hormone (LH) secretion has not yet been elucidated, but recent evidence has suggested that arachidonic acid or its metabolites are involved in GnRH action. In cultured rat pituitary cells, arachidonic acid and 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) elicited concentration-dependent release of LH with EC50 of about 12μM. Other lipoxygenase derivatives including 11-, 12- and 15-HETE, had no consistent effect on LH release, and leukotrienes (B4 and C4) exerted only minor stimulatory actions on LH release. The lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA), 5,8,11,14-eicosatetraynoic acid (ETYA), and 3-amino-1-(3-trifluoromethyl phenyl)-2-pyrazoline hydrochloride (BW 755C) caused dose-dependent inhibition of GnRH-induced LH release, with IC50 values of 5, 8.5, and 175μM, respectively. In contrast, the cyclooxygenase inhibitor, indomethacin, had a biphasic action on GnRH-stimulated LH release, with potentiation of GnRH action at low doses (up to 25 μM) and no effect at higher concentrations. These findings are consistent with the potential role of a 5-lipoxygenase product of arachidonic acid in the mechanism of action of GnRH on pituitary gonadotropin release.

Original languageEnglish
Pages (from-to)711-717
Number of pages7
JournalJournal of Steroid Biochemistry
Volume23
Issue number5 PART 2
DOIs
StatePublished - Nov 1985
Externally publishedYes

Keywords

  • 11-HETE
  • 11-hydroxy-5,8,12,14-eicosatetraenoic acid
  • 12-HETE
  • 12-hydroxy-5,8,10,14-eicosatetraenoic acid
  • 15-HETE
  • 15-hydroxy-5,8,10,14-eicosatetraenoic acid
  • 3-amino-1-(3-trifluoromethyl phenyl)-2-pyrazoline hydrochloride
  • 4-(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid
  • 5,8,11,14-eicosatetraenoic acid
  • 5-HETE
  • 5-HPETE
  • 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid
  • 5-hydroxy-6,8,11,14-eicosatetraenoic acid
  • BW 755C
  • ETYA
  • FSH
  • GnRH
  • Hepes
  • LH
  • LTB
  • LTC
  • NDGA
  • PA
  • PG's
  • PGG
  • PGH
  • PI
  • adenosine 3′,5′-cyclic monophosphoric acid
  • cAMP
  • cGMP
  • follicle stimulating hormone
  • gonadotropin-releasing hormone
  • guanosine 3′,5′-cyclic monophosphoric acid
  • leukotriene B
  • leukotriene C
  • luteinizing hormone
  • nordihydroguaiaretic acid
  • phosphatidic acid
  • phosphatidylinositol
  • prostaglandin G
  • prostaglandin H
  • prostaglandins

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