title: Supraphysiological level of estrogen exposure in vivo increases lymphoid cell death in mice.
abstract: Estrogen can enhance or reduce lymphocyte functions in vitro depending on dose and exposure duration. The purpose of this study was to determine the effect of in vivo 17 beta-estradiol (E2) on apoptosis and necrosis in lymphoid tissue of female C567BL/6 mice. Animals were ovariectomized (OVX), ovariectomized and 17 beta-estradiol supplemented (OVX + E2; 71 micrograms E2 per day for 14 days), sham ovariectomized (SHAM), or unhandled controls (CONTROL). Thymus and spleen were removed aseptically, cells dispersed into single cell suspensions in RPMI-1640, and measures of cell damage performed: an annexin V flow cytometric assay for markers of apoptosis and an enzyme-linked immunoassay for measures of DNA fragmentation and necrosis. OVX + E2 mice had 620 +/- 72 pg/ml 17 beta-estradiol in serum in contrast to OVX mice which had 7.6 +/- 5 pg/ml, the SHAM mice which had 2.8 +/- 1 pg/ml of serum E2, and the CONTROL mice which had 3.9 +/- 0.8 pg/ml of serum E2 (p < 0.001). There was a significantly lower percentage of viable thymocytes in OVX + E2 mice compared to the other treatment conditions (p < 0.001, respectively). There was also a significantly higher percentage of annexin V positive thymocytes in OVX + E2 mice (p < 0.005). Measures of DNA fragmentation by ELISA were higher in splenocytes from OVX + E2 mice than in the OVX, SHAM or CONTROL mice (p < 0.005). These results suggest that supraphysiological levels of estrogen in vivo induce damage in lymphoid cells; however, the impact of estrogen associated lymphoid tissue damage on specific immune functions remains to be determined.
authors.affiliation: Department of Health Studies and Gerontology, University of Waterloo, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Zajchowski
authors.forename: L
authors.initials: L
authors.lastname: Hoffman-Goetz
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008221:Lymphoid Tissue / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D010052:Ovariectomy; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
chemical_list: D017304:Annexin A5; D004958:Estradiol