Expression of cyclooxygenase enzymes in rat hypothalamo-pituitary-adrenal axis: effects of endotoxin and glucocorticoids.
Prostaglandins play a key role in mediating the hypothalamo-pituitary-adrenocortical (HPA) responses to immune insults. This study aimed to provide some insight into the relative contributions of the constitutive and inducible forms of cyclooxygenase (COX-1 and COX-2) to the generation of these prostanoids by examining the effects of (1) endotoxin treatment on the expression of COX-1 and COX-2 mRNAs in the various components of the HPA axis in control and glucocorticoid pretreated rats, and (2) selective inhibition of COX-2 on the production of corticosterone by adrenal tissue in vitro. Endotoxin caused a marked rise in COX-2 mRNA in the adrenal gland that was evident 3 and 6 h after the injection and was prevented by pretreatment with dexamethasone. It also induced a modest increase in COX-2 mRNA in the hypothalamus but not in the hippocampus or anterior pituitary gland. By contrast, COX-1 mRNA was largely unaffected by the drug treatments in all tissues studied. In vitro the selective COX-2 inhibitor SC-236 caused a marked reduction in adrenocorticotropic hormone-driven corticosterone release, as did the nonselective COX inhibitor, indomethacin. These results support a role of COX-2 in the manifestation of the HPA responses to endotoxin, particularly within the adrenal gland.
Cover
P O
PO
Department of Neuroendocrinology, Imperial College of Science Technology and Medicine, Hammersmith Hospital, London. p.cover@ic.ac.uk
Slater
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Buckingham
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JC
D000818:Animals; D003345:Corticosterone / Q000096:biosynthesis; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000201:enzymology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D010913:Pituitary-Adrenal System / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
D003345:Corticosterone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D005938:Glucocorticoids; D007213:Indomethacin; D007527:Isoenzymes; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C496513:Ptgs1 protein, rat