title: Protection from lethal endotoxic shock after testosterone depletion is linked to chromosome X.
abstract: Men are considered more susceptible to sepsis after severe injury than are women, which has been attributed to a suppressing effect of male sex steroids on the inflammatory response. Moreover, the effect of sex steroids on the inflammatory process depends on the genetic background. The present study examined the genetic contribution to survival after endotoxic shock in mice depleted of testosterone by surgical castration. Six-week-old male mice, from strains A/J, AKR/J, C57BL/6J (B6), BALBc/J, DBA/2J, and C3H/HeN, were castrated (CX) or nonoperated (NoOp). Two weeks after surgery, mice were injected intraperitoneally with Escherichia coli lipopolysaccharide (15 mg/kg) and the frequency of mortality was monitored. CX A/J mice showed a significantly higher survival rate than NoOp mice, but this protective effect was not observed in the other strains. Administration of 5-alpha-dihydrotestosterone to CX A/J mice reverted the protection by CX. The protective effect of CX was also observed in crosses of female A/J and male B6 (AXB), but not female B6 and male A/J (BXA), suggesting that protection is linked to the A/J X chromosome. This possibility was corroborated by using consomic mice containing A/J chromosome X and the remaining chromosomes from B6. These results suggest that testosterone is a negative factor in the recovery from endotoxic shock, depending on the genetic background.
authors.affiliation: Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Manuel B
authors.initials: MB
authors.lastname: Torres
authors.forename: Heiko
authors.initials: H
authors.lastname: Trentzsch
authors.forename: Dylan
authors.initials: D
authors.lastname: Stewart
authors.forename: Maria Lourdes
authors.initials: ML
authors.lastname: Mooney
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Fuentes
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Saad
authors.forename: Roger H
authors.initials: RH
authors.lastname: Reeves
authors.forename: Antonio
authors.initials: A
authors.lastname: De Maio
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D004967:Estrogens / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012772:Shock, Septic / Q000235:genetics* / Q000401:mortality / Q000517:prevention & control*; D013739:Testosterone / Q000097:blood / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014945:Wound Healing; D014960:X Chromosome
chemical_list: D004967:Estrogens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013739:Testosterone