Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus.
The fever response is blunted at near term. As the enzyme cyclooxygenase-2 (COX-2) plays a critical role in fever development, we measured its expression in rat hypothalamus during pregnancy and lactation. Western blot analysis revealed a 72-kDa COX-2-immunoreactive band in non-immune-challenged, pregnant rats at day 15 of pregnancy. In contrast, it was almost undetectable at near term and at lactation day 5. COX-2 was significantly induced at the 15th day of pregnancy and at the 5th lactating day after intraperitoneal lipopolysaccharide (50 microg/kg). However, this COX-2 induction was significantly reduced at near term compared with values before and after term. The protein levels of the EP3 receptor in the hypothalamus, one of the prostaglandin E(2) (PGE(2)) receptors suggested to be a key receptor for fever induction, were unaffected throughout the pregnancy and lactation in both non-immune-challenged and lipopolysaccharide-treated rats. These data suggest that suppression of fever at near term is associated with a significantly reduced induction of COX-2 by lipopolysaccharide, resulting in a reduced production of PGE(2). Altered expression of the EP3 receptor does not seem to be involved in this fever refractoriness at near term.
Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Alberta, T2N 4N1 Canada. mouihate@ucalgary.ca
A
A
Mouihate
M-S
MS
Clerget-Froidevaux
K
K
Nakamura
M
M
Negishi
J L
JL
Wallace
Q J
QJ
Pittman
D000818:Animals; D051546:Cyclooxygenase 2; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D007031:Hypothalamus / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism*; D007743:Labor, Obstetric / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype
D007527:Isoenzymes; D008070:Lipopolysaccharides; C545649:Ptger3 protein, rat; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases