HPTE-Induced Embryonic Thymocyte Death and Alteration of Differentiation Is Not Rescued by ERα or GPER Inhibition but Is Exacerbated by Concurrent TCR Signaling.
HPTE-Induced Embryonic Thymocyte Death and Alteration of Differentiation Is Not Rescued by ERα or GPER Inhibition but Is Exacerbated by Concurrent TCR Signaling.
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DOI：
10.3390/ijms221810138
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发表时间：
2021-09-20
影响因子：
5.6
通讯作者：
Broussard C
中科院分区：
文献类型：
--
作者：
Avellaneda E;Lim A;Moeller S;Marquez J;Escalante Cobb P;Zambrano C;Patel A;Sanchez V;Godde K;Broussard C
有机氯农药，如滴滴涕、甲氧氯及其代谢物，已被定性为内分泌干扰化学品（EDCs）；提示它们的作用方式涉及与内源性内分泌功能的相互作用或废止。本研究探讨甲氧基氯初级代谢物HPTE诱导的胚胎胸腺细胞死亡和分化改变是否依赖于雌激素受体结合和同步T细胞受体信号传导。雌激素受体ERα或GPER抑制不能挽救HPTE或模型雌激素己烯雌酚（DES）诱导的胚胎胸腺细胞死亡。此外，与EDC暴露后的TCR和CD2分化信号相比，HPTE或DES诱导的不良反应在并发TCR和CD2分化信号下加重。总之，这些数据表明，HPTE和des对胚胎胸腺细胞的不良影响并不仅仅依赖于ER α或GPER，而可能需要两者。这些结果也为TCR和雌激素受体之间潜在的协同信号传导机制提供了证据，以介导对胚胎胸腺细胞的不良影响，并强调了调节EDC暴露严重程度的敏感性窗口。
Organochlorine pesticides, such as DDT, methoxychlor, and their metabolites, have been characterized as endocrine disrupting chemicals (EDCs); suggesting that their modes of action involve interaction with or abrogation of endogenous endocrine function. This study examined whether embryonic thymocyte death and alteration of differentiation induced by the primary metabolite of methoxychlor, HPTE, rely upon estrogen receptor binding and concurrent T cell receptor signaling. Estrogen receptor inhibition of ERα or GPER did not rescue embryonic thymocyte death induced by HPTE or the model estrogen diethylstilbestrol (DES). Moreover, adverse effects induced by HPTE or DES were worsened by concurrent TCR and CD2 differentiation signaling, compared with EDC exposure post-signaling. Together, these data suggest that HPTE- and DES-induced adverse effects on embryonic thymocytes do not rely solely on ER alpha or GPER but may require both. These results also provide evidence of a potential collaborative signaling mechanism between TCR and estrogen receptors to mediate adverse effects on embryonic thymocytes, as well as highlight a window of sensitivity that modulates EDC exposure severity.
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影响因子：
6.1
作者：
Adam AHB;de Haan LHJ;Estruch IM;Hooiveld GJEJ;Louisse J;Rietjens IMCM
通讯作者：
Rietjens IMCM
DOI：
10.1093/toxsci/kfn141
发表时间：
2008-10
期刊：
Toxicological sciences : an official journal of the Society of Toxicology
影响因子：
--
作者：
Sotoca AM;van den Berg H;Vervoort J;van der Saag P;Ström A;Gustafsson JA;Rietjens I;Murk AJ
通讯作者：
Murk AJ
影响因子：
2.2
作者：
Brown, N;Nagarkatti, M;Nagarkatti, PS
通讯作者：
Nagarkatti, PS
影响因子：
4.8
作者：
Gaido, KW;Leonard, LS;Safe, S
通讯作者：
Safe, S
影响因子：
--
作者：
BLAND, JM;ALTMAN, DG
通讯作者：
ALTMAN, DG