Production of leukotrienes in gonadotropin-releasing hormone-stimulated pituitary cells: potential role in luteinizing hormone release.
Gonadotropin-releasing hormone (GnRH) stimulated the formation of two major metabolites of the 5-lipoxygenase pathway, leukotriene (LT) B4 and LTC4, as well as luteinizing hormone (LH) release in primary cultures of rat anterior pituitary cells. Several lines of evidence suggested the presence of a GnRH-dependent pituitary endocrine system in which LTs act as second messengers for LH release: (i) GnRH-dependent LT formation was observed within 1 min and immediately preceded GnRH-induced LH release, whereas exogenous LTs stimulated LH release at low concentrations; (ii) the dose responses of GnRH-induced LT production and LH release were similar and both effects required the presence of extracellular Ca2+ ions; (iii) GnRH-induced LH release was blocked by up to 45% following the administration of several LT receptor antagonists; (iv) LTE4 action on LH secretion was entirely abolished by LT receptor antagonists; and (v) an activator of protein kinase C acted synergistically with LTE4 to induce LH release. The major source of LT formation in the pituitary cell cultures appeared to be the gonadotrophs, as shown by GnRH receptor desensitization experiments. The results demonstrate the presence of a GnRH-activatable 5-lipoxygenase pathway in anterior pituitary cells and provide strong support for the hypothesis that LTs play a role in LH release in the GnRH signaling pathway.
Kiesel
L
L
Department of Obstetrics and Gynecology, University of Heidelberg, Federal Republic of Germany.
Przylipiak
A F
AF
Habenicht
A J
AJ
Przylipiak
M S
MS
Runnebaum
B
B
D000818:Animals; D002118:Calcium / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000502:physiology*; D017999:Leukotriene E4; D007986:Luteinizing Hormone / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011966:Receptors, LHRH / Q000378:metabolism; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D011966:Receptors, LHRH; D013189:SRS-A; D007975:Leukotriene B4; D007987:Gonadotropin-Releasing Hormone; D017999:Leukotriene E4; D007986:Luteinizing Hormone; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium