Effect of estradiol and exercise on lymphocyte proliferation responses in female mice

Many North American women are encouraged to take estrogen replacement therapy and to begin (or continue) physical activity during the postmenopausal years. This study investigated the effect of estradiol exposure and physical exercise on lymphocyte proliferation responses to T and B cell mitogens in female mice. Sixty C57BL/6 mice were randomized to hormone and exercise treatment conditions: hormone treatment consisted of estradiol in vivo (71.4 microg estradiol per day for 21 days) or placebo pellet following bilateral ovariectomy, or surgical sham (mice were not ovariectomized). Exercise consisted of a single forced treadmill run (26 m/min, 6 degrees slope, 90 min) or a sedentary control condition. Outcomes were thymic and splenic lymphocyte proliferation responses to the mitogens concanavalin A (ConA, 1.0 and 5.0 microg/mL concentrations) and lipopolysaccharide (LPS, 0.5, 1.0, and 2.0 microg/mL concentrations). In the thymus, there was a significant reduction of proliferation to ConA in the Ovx + E2 animals relative to the other conditions at both concentrations of mitogen. At 1.0 microg/mL concentration, there was a significant interaction of hormone and exercise treatments. Sham (control) mice given exercise had a higher proliferation response relative to sedentary counterparts, whereas E2 mice did not differ in proliferation responses, irrespective of exercise condition. In the spleen, exposure to high concentrations of estradiol was associated with reduced proliferation responses to both mitogens; there were, however, no main or interaction effects of exercise. These results suggest that high levels of estradiol exposure following ovariectomy in mice significantly reduces lymphocyte blastogenesis responses, and that thymic immunomodulation after acute exercise is masked by the hormonal effect.