testosterone and shock


Shock. 2005 Oct;24(4):318-323


PROTECTION FROM LETHAL ENDOTOXIC SHOCK AFTER TESTOSTERONE DEPLETION IS
LINKED TO CHROMOSOME X.

Torres MB, Trentzsch H, Stewart D, Mooney ML, Fuentes JM, Saad DF, Reeves
RH, Maio AD.

*Division of Pediatric Surgery and daggerDepartment of Physiology, Johns
Hopkins University School of Medicine, Baltimore, MD.

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.

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