Effects of Estrogen on Gender Differences in Susceptibility to HSV-1 Infection Following Exhaustive Exercise Stress

Abstract

0907 Fatiguing exercise increases susceptibility to respiratory infection following intranasal inoculation with herpes simplex virus-1 (HSV-1) in male mice (Davis et al, JAP, 83: JAP 1461–1466, 1997). However, female mice appear to be less susceptible to the lethal effects of HSV-1 infection than males (unpublished). Circulating estrogen may account for this observed protection from death in female mice. PURPOSE: To test whether estrogen is responsible for gender differences in HSV-1 infection following exercise stress. METHODS: CD-1 mice (∼50 d old) were randomly assigned to either exercise (Ex) or control (C) groups (n = 21–23): male (M-Ex or M-C), female (F-Ex or F-C), ovariectomized female (O-Ex or O-C), and ovariectomized plus estrogen (E2-Ex or E2-C). Estrogen treatment consisted of an implanted pellet to release a constant physiological dose of 17-β estradiol for 34 days (∼1μg/day). Exercise consisted of 3 days of running at 36 m/min, 8% grade until volitional fatigue. Fifteen min following the last bout of exercise, all mice were inoculated intranasally with a standard dose (LD40) of HSV-1. Mice were monitored for 21 days for morbidity (time to sickness and symptom severity) and mortality. RESULTS: F-Ex run time to fatigue was significantly longer than M-Ex and O-Ex ran longer than E2-Ex (p < 0.05). F had a later time to death than M, O, and E2 (p < 0.05). F had significantly fewer deaths than both O and E2 in both Ex and C (p < 0.05). Ex resulted in increased time to sickness in all groups (p < 0.05), but no differences in overall mortality or symptom severity as we have previously observed in younger mice. CONCLUSION: Results indicate that intact female mice are better protected from the lethal effects of HSV-1 infection than males. This protective effect was lost in ovariectomized mice and it was not reinstated by estrogen replacement. This suggests that the protective effect in intact female mice is not due solely to stable physiologic levels of estrogen, at least in this model. Further research is warranted to determine the effects of progesterone alone or in combination with estrogen on susceptibility to HSV-1 infection in female mice. Supported by an ACSM student grant.