title: Sex steroid regulation of macrophage migration inhibitory factor in normal and inflamed colon in the female rat.
abstract: OBJECTIVE
  Sex steroids influence IBD symptoms. Macrophage migration inhibitory factor (MIF), a target of sex steroids in other inflammatory models, promotes interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha release in colitis. We investigated whether estradiol and progesterone influence MIF, IL-1beta, and TNF-alpha production in experimental colitis.
  
  
  METHODS
  Colonic MIF, IL-1beta, and TNF-alpha levels were measured in cyclic and ovariectomized rats, with or without estradiol benzoate (EB) or progesterone (P) replacement. MIF distribution was assessed by immunohistochemistry. Cytokines, myeloperoxidase activity, macroscopic damage, and plasma corticosterone were assessed 24 hours after intrarectal trinitrobenzene sulfonic acid (TNBS), with and without neutralizing anti-MIF antibody. Effects of EB and P on myeloperoxidase activity and MIF concentration were also assessed at 7 days in dextran sulfate sodium-induced colitis.
  
  
  RESULTS
  Basal IL-1beta and TNF-alpha contents did not fluctuate during the estrous cycle, while MIF concentrations increased from estrus (estrogen dominance) to metestrus (P dominance; P < .05). EB and P treatment mimicked these effects in ovariectomized rats, and similarly altered MIF immunostaining. Progesterone dominance aggravated TNBS colitis in comparison with estrogen. Progesterone enhanced TNBS-induced MIF (P < .001) and TNF-alpha (P < .01) production, while EB decreased MIF (P < .01) and IL-beta levels (P < .01). Anti-MIF antibody prevented P-mediated up-regulation of TNF-alpha, improved TNBS colitis, and enhanced plasma corticosterone. At 7 days after dextran sulfate sodium, EB decreased myeloperoxidase activity and MIF concentration, while P had no effect.
  
  
  CONCLUSIONS
  Estrogen decreases while progesterone increases MIF production in the female rat colon. Changes in basal MIF contents may affect colon susceptibility to inflammation, by modulating TNF-alpha and IL-1beta production during early stages of colitis.
authors.affiliation: Neuro-Gastroenterology and Nutrition Unit, Institut National de la Recherche Agronomique, Toulouse, France. eric.houdeau@toulouse.inra.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Houdeau
authors.forename: Raphael
authors.initials: R
authors.lastname: Moriez
authors.forename: Mathilde
authors.initials: M
authors.lastname: Leveque
authors.forename: Christel
authors.initials: C
authors.lastname: Salvador-Cartier
authors.forename: Aurelie
authors.initials: A
authors.lastname: Waget
authors.forename: Lin
authors.initials: L
authors.lastname: Leng
authors.forename: Lionel
authors.initials: L
authors.lastname: Bueno
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: Jean
authors.initials: J
authors.lastname: Fioramonti
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003345:Corticosterone / Q000097:blood; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D010052:Ovariectomy; D009195:Peroxidase / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D012737:Sex Factors; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D012739:Gonadal Steroid Hormones; D053583:Interleukin-1beta; D008263:Macrophage Migration-Inhibitory Factors; D014409:Tumor Necrosis Factor-alpha; C074283:estradiol 3-benzoate; D011374:Progesterone; D004958:Estradiol; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D009195:Peroxidase; D019746:Intramolecular Oxidoreductases; C515599:Mif protein, rat; D003345:Corticosterone