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

The etiology of autoimmune thyroid diseases is unclear; however, the extreme female predominance suggests that sex hormones may have a pathogenic role. 2-Methoxyestradiol (2-ME) is present in the serum of women during the ovulatory and luteal phases of the menstrual cycle, and during pregnancy. We i...

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Veröffentlicht in:Molecular and cellular endocrinology 2000-07, Vol.165 (1), p.163-172
Hauptverfasser: Wang, S.H, Myc, A, Koenig, R.J, Bretz, J.D, Arscott, P.L, Baker, J.R
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container_end_page 172
container_issue 1
container_start_page 163
container_title Molecular and cellular endocrinology
container_volume 165
creator Wang, S.H
Myc, A
Koenig, R.J
Bretz, J.D
Arscott, P.L
Baker, J.R
description The etiology of autoimmune thyroid diseases is unclear; however, the extreme female predominance suggests that sex hormones may have a pathogenic role. 2-Methoxyestradiol (2-ME) is present in the serum of women during the ovulatory and luteal phases of the menstrual cycle, and during pregnancy. We investigated 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 thyroid follicles. Flow cytometric analysis showed that 2-ME halted cell proliferation by arresting the cells in the G2/M cell-cycle compartment. Prolonged exposure to 2-ME led to apoptosis and to increased release of the autoantigen thyroid peroxidase (TPO). 17β-estradiol failed to produce a similar effect even in 40-fold molar excess to 2-ME. Co-treatment with estrogen receptor antagonists did not alter the 2-ME effect, indicating that 2-ME was not operating through a classic nuclear estrogen receptor. In conclusion, this study indicates that 2-ME induces G2/M cycle arrest, apoptosis and the disruption of thyroid follicles. This process results in the release of thyroid antigens that may play a role in high incidence of thyroid autoantibodies and autoimmune thyroid disease in women.
doi_str_mv 10.1016/S0303-7207(00)00249-5
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We investigated 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 thyroid follicles. Flow cytometric analysis showed that 2-ME halted cell proliferation by arresting the cells in the G2/M cell-cycle compartment. Prolonged exposure to 2-ME led to apoptosis and to increased release of the autoantigen thyroid peroxidase (TPO). 17β-estradiol failed to produce a similar effect even in 40-fold molar excess to 2-ME. Co-treatment with estrogen receptor antagonists did not alter the 2-ME effect, indicating that 2-ME was not operating through a classic nuclear estrogen receptor. In conclusion, this study indicates that 2-ME induces G2/M cycle arrest, apoptosis and the disruption of thyroid follicles. 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subjects 2-Methoxyestradiol
Animals
Apoptosis
Apoptosis - drug effects
Autoantigens - metabolism
Cell cycle
Cell Cycle - drug effects
Cells, Cultured
Estradiol - analogs & derivatives
Estradiol - metabolism
Estradiol - pharmacology
Estrogen
Estrogens - metabolism
Female
Humans
Iodide Peroxidase - immunology
Iodide Peroxidase - metabolism
Male
Pregnancy
Rats
Thyrocyte
Thyroid Gland - cytology
Thyroid Gland - drug effects
Thyroiditis, Autoimmune - etiology
title 2-Methoxyestradiol, an endogenous estrogen metabolite, induces thyroid cell apoptosis
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