Meeting Abstract

P1.211  Friday, Jan. 4  Estradiol induces thymus gland apoptosis via both estrogen and glucocorticoid receptor pathways in Xenopus laevis tadpoles MCCAFFREY, A*; GARCIA, J; PRIYAMVADA, L; YAO, A; HECKMAN, K; SCHREIBER, A; St. Lawrence University; St. Lawrence University; St. Lawrence University; St. Lawrence University; St. Lawrence University; St. Lawrence University aschreiber@stlawu.edu

Similar to the suppressive effects of glucocorticoids on the immune system, high levels of endogenously-produced or exogenously-administered estrogen are known to cause the thymus to atrophy in mammals. However, the influence of estrogen and estrogenic compounds on thymus gland development in tadpoles and other aquatic vertebrates remains unknown. Here we show that treatment of young tadpoles (7 days-post fertilization; Nieuwkoop and Faber stage 50) for 6 days with estradiol (10 uM), or dexamethasone (DEX, 2 uM; a glucocorticoid receptor agonist) significantly reduces thymus gland size by 35%, and 67%, respectively. Treatment of tadpoles with estradiol induces maximum active caspase-3 expression (a mediator of programmed cell death) in thymocytes within 48-72 hours, after which levels of thymus cell apoptosis decrease. Compared with tadpoles treated with DEX alone, those treated with DEX + RU-486 (200 nM; a glucocorticoid receptor antagonist) completely rescued tadpoles from reduction in thymus size. In contrast, treatment of tadpoles with estradiol (10 uM ) + fulvestrant (25 uM; an estrogen receptor-specific antagonist) only resulted in a partial rescue of the estradiol-induced reduction in thymus size. Interestingly, treatment of tadpoles with estradiol + RU-486 also produced a partial rescue of the estradiol-induced reduction in thymus size. These findings suggest that some of the effects of estradiol and estrogenic compounds (such as bisphenol-A and atrazine) on thymus gland apoptosis may be mediated by a concurrent activation by estrogenic substances of the glucocorticoid stress-response pathway.