Endotoxin stimulates in vitro pituitary growth hormone release in eicosanoid-dependent manner.
OBJECTIVE
To investigate the signal transduction pathways by which endotoxin stimulates in vitro pituitary cell growth hormone (GH) release.


METHODS
Pituitary cell cultures derived from 6 sheep.


METHODS
Signal transduction pathways involved in endotoxin-mediated GH release from sheep pituitary cell cultures were evaluated by the use of specific blockers of arachidonic acid and its metabolites, extracellular calcium, protein kinase C, and protein kinase A. Cell cultures were exposed to the specific blockers in the presence or absence of endotoxin (Escherichia coli O55:B5, 10 micrograms/ml) for 24 hours. In addition, effects of endotoxin on GH cell content and GH mRNA values were determined.


RESULTS
Nordihydroquairetic acid (lipoxygenase blocker, 10 microM, 30 microM) and eicosatetraynoic acid (arachidonic acid competitor, 10 microM) decreased endotoxin-stimulated GH release. The calcium channel blocker verapamil (25 microM) decreased baseline and endotoxin-stimulated GH release. Phorbol myristate acetate-induced down-regulation of protein kinase C, indomethacin, or the protein kinase A blocker H89 did not alter endotoxin-stimulated GH release. Endotoxin increased GH mRNA values by 50.1 +/- 6.0%, but the cell content of GH was not affected.


CONCLUSIONS
A direct effect of endotoxin on the pituitary gland to stimulate GH secretion was evident, an effect mediated predominantly by arachidonic acid and its metabolites through the lipoxygenase pathway. Endotoxin-stimulated GH release requires extracellular calcium and is associated with increased cell GH mRNA content.


CONCLUSIONS
A better understanding of the signal transduction pathways involved in endotoxin-mediated effects will allow more appropriate therapeutic intervention in clinical cases of endotoxemia.
Coleman
E S
ES
Department of Anatomy, School of Veterinary Medicine, Tuskegee University, AL 36088, USA.
Sartin
J L
JL
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors; D002121:Calcium Channel Blockers / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D004731:Endotoxins; D016859:Lipoxygenase Inhibitors; D015117:5,8,11,14-Eicosatetraynoic Acid; D009637:Masoprocol; D013006:Growth Hormone; D014700:Verapamil; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin