2-Methoxyestradiol, an endogenous estrogen metabolite, induces thyroid cell apoptosis

The etiology of autoimmune thyroid diseases is unclear; however, the extrem e female predominance suggests that sex hormones may have a pathogenic role . 2-Methoxyestradiol (2-ME) is present in the serum of women during the ovu latory and luteal phases of the menstrual cycle, and during pregnancy. We i nvestigated the actions of 2-ME and estrogen on thyroid follicular cells. 2 -ME induced dramatic changes in cell morphology and decreased the viability of the cells, as well as disrupted the structural integrity of cultured th yroid follicles. Flow cytometric analysis showed that 2-ME halted cell prol iferation by arresting the cells in the G2/M cell-cycle compartment. Prolon ged exposure to 2-ME led to apoptosis and to increased release of the autoa ntigen thyroid peroxidase (TPO). 17 beta-estradiol failed to produce a simi lar effect even in 40-fold molar excess to 2-ME. Go-treatment with estrogen receptor antagonists did not alter the 2-ME effect, indicating that 2-ME w as not operating through a classic nuclear estrogen receptor. In conclusion , this study indicates that 2-ME induces G2/M cycle arrest, apoptosis and t he disruption of thyroid follicles. This process results in the release of thyroid antigens that may play a role in high incidence of thyroid autoanti bodies and autoimmune thyroid disease in women. (C) 2000 Elsevier Science I reland Ltd. All rights reserved.