Effect of 17beta-estradiol and voluntary exercise on lymphocyte apoptosis in mice.
During the perimenopause, women may begin estrogen replacement therapy (ERT) and physical activity programs to reduce the symptoms of the climacteric. High-intensity exercise increases lymphocyte apoptosis, and estrogen is also known to have immune modulatory effects. The present study determined whether (1) estrogen exposure in vivo, and (2) low-intensity, voluntary exercise affect thymic and splenic lymphocyte apoptosis in adult female mice. 'Middle-aged' (>1 year), ovarian-intact female B6D2F(1) mice were implanted with 17beta-estradiol (E) pellets (L: 3 microg/day or H: 12 microg/day) or placebo (P: 0 microg/day). Mice were given 1 week to recover from implantation surgery after which they were randomized to wheel-running or no-wheel-running conditions. Twenty one days later, mice were sacrificed and thymus and spleen removed for determination of percent apoptosis and percent necrosis by flow cytometry, serum E levels by RIA, and tissue and body weights. Estrogen-treated, ovarian-intact mice accumulated less cumulative wheel-running activity than mice implanted with placebo (P<.001). E exposure was associated with lighter thymuses (P<.05), higher thymocyte apoptosis (P<.001), and higher serum E levels (P<.001), effects which were not modified by voluntary exercise. In contrast, splenocyte apoptosis and spleen weights did not differ by estrogen treatment or exercise. The results suggest that in vivo exposure to supplemental estrogen is associated with greater spontaneous apoptosis of thymocytes and reduced thymus weights in older ovarian-intact mice. The clinical significance for thymic (cellular) immunity in perimenopausal women given HRT remains to be determined.
Hoffman-Goetz
L
L
Department of Health Studies and Gerontology, Faculty of Applied Health Sciences, University of Waterloo, N2L 3G1, Waterloo, Ontario, Canada. lhgoetz@healthy.uwaterloo.ca
Fietsch
C L
CL
McCutcheon
D
D
Duerrstein
L
L
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D005082:Physical Exertion / Q000502:physiology*
D004958:Estradiol