DES action in the thymus: inhibition of cell proliferation and genetic variation

Many tissues, including the thymus, represent direct targets of estrogen action. In contrast to many estrogen responsive tissues, the thymus undergoes a profound atrophy in response to elevated levels of estrogens. The mechanism of estrogen-induced atrophy in the thymus is unknown; however, it appears not to involve massive thymocyte apoptosis. Here, we demonstrate that the estrogen diethylstilbestrol (DES) inhibits cell proliferation within the thymic cortex, the primary site of thymocyte proliferation. Unlike glucocorticoid action, the effect of DES on thymocyte proliferation does not appear to be mediated by direct down regulation of cyclin D3. We also demonstrate for the first time that rat strains vary in their sensitivity to DES-induced thymic atrophy. This sensitivity correlates with the ability of DES to inhibit cell proliferation in the thymus. These data suggest that genetic factors may regulate estrogen action within this tissue by affecting estrogen responsive pathways that control cell proliferation.