Prostaglandins mediate lipopolysaccharide effects upon cholecystokinin and neurotensin phenotypes in neuroendocrine corticotropin-releasing hormone neurons: in situ hybridization evidence in the rat.
Intraperitoneal injection of the endotoxin lipopolysaccharide produces an inflammation accompanied by immune system activation and secretion of cytokines that stimulate the hypothalamo-pituitary-adrenal (HPA) axis to release the anti-inflammatory corticosterone. Upstream in HPA axis are neuroendocrine corticotropin-releasing hormone neurons in the paraventricular nucleus whose multipeptidergic phenotype changes during inflammation: coexisting corticotropin-releasing hormone and cholecystokinin mRNAs are up-regulated whereas neurotensin mRNA expression is induced de novo. These changes may be mediated by prostaglandins released from perivascular and microglial cells in response to circulating cytokines. We examined by quantitative in situ hybridization histochemistry whether blockade of prostaglandin synthesis by indomethacin alters phenotypic expression in paraventricular nucleus neurons after lipopolysaccharide. Because indomethacin also elevated circulating corticosterone, animals were adrenalectomized and corticosterone replaced. Results showed that i.p. indomethacin administration suppressed lipopolysaccharide effects in a phenotype non-specific manner: one injection was sufficient to prevent both the increase in corticotropin-releasing hormone and cholecystokinin mRNAs expression and the induction of neurotensin mRNA expression. Therefore, neuroendocrine corticotropin-releasing hormone neurons with different peptidergic phenotypes appear to respond as a whole in the acute phase response to systemic infection.
Ribot
E
E
Laboratoire des Régulations Neuroendocriniennes, EA2972, Université Bordeaux 1, Avenue des Facultés, 33405 Talence, France. elodie.ribot@etu.u-bordeaux1.fr
Lafon
P
P
Ciofi
P
P
Sarrieau
A
A
Tramu
G
G
Corio
M
M
D000315:Adrenalectomy; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002766:Cholecystokinin / Q000187:drug effects / Q000378:metabolism*; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D017403:In Situ Hybridization; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009496:Neurotensin / Q000187:drug effects / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010641:Phenotype; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D011453:Prostaglandins; D009496:Neurotensin; D002766:Cholecystokinin; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone; D007213:Indomethacin