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Expression of cyclooxygenase enzymes in rat hypothalamo-pituitary-adrenal axis

Effects of endotoxin and glucocorticoids

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Abstract

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.

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Authors and Affiliations

  1. Department of Neuroendocrinology, Faculty of Medicine, Division of Neuroscience and Psychological Medicine, Imperial College of Science Technology and Medicine, Commonwealth Building, Hammersmith Hospital, Du Cane Road, W12 0NN, London

    Patricia O. Cover

  2. Department of Biological Sciences, The University of Warwick, Gibbet Hill, Coventry

    Donna Slater

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Cover, P.O., Slater, D. & Buckingham, J.C. Expression of cyclooxygenase enzymes in rat hypothalamo-pituitary-adrenal axis. Endocr 16, 123–131 (2001). https://doi.org/10.1385/ENDO:16:2:123

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  • DOI: https://doi.org/10.1385/ENDO:16:2:123

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