A computational model to predict rat ovarian steroid secretion from in vitro experiments with endocrine disruptors.
A computational model to predict rat ovarian steroid secretion from in vitro experiments with endocrine disruptors.
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DOI：
10.1371/journal.pone.0053891
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bois FY
中科院分区：
文献类型：
--
作者：
Quignot N;Bois FY
雌激素和雄激素之间微调的平衡控制着生殖功能，而类固醇合成的最后一步在维持这种平衡方面起着关键作用。环境毒物是一个严重的健康问题，许多研究致力于研究内分泌干扰物(EDCs)的影响。内分泌细胞对类固醇产生酶的作用可能影响类固醇的分泌，从而导致生殖毒性。为了根据体外获得的颗粒细胞芳香酶活性和mRNA水平调节的数据来预测激素平衡紊乱，我们建立了性激素合成途径的性腺最后步骤的数学模型。该模型可以模拟卵巢合成和分泌雌酮、雌二醇、雄烯二酮和睾酮，以及它们对内分泌干扰的反应。该模型能够预测正常发情周期下雌性大鼠的卵巢性类固醇浓度，以及暴露于阿特拉津、双酚A、甲氧氯胺或长春花碱代谢物和来曲唑的成年雌性大鼠的卵巢雌二醇浓度。
A finely tuned balance between estrogens and androgens controls reproductive functions, and the last step of steroidogenesis plays a key role in maintaining that balance. Environmental toxicants are a serious health concern, and numerous studies have been devoted to studying the effects of endocrine disrupting chemicals (EDCs). The effects of EDCs on steroidogenic enzymes may influence steroid secretion and thus lead to reproductive toxicity. To predict hormonal balance disruption on the basis of data on aromatase activity and mRNA level modulation obtained in vitro on granulosa cells, we developed a mathematical model for the last gonadal steps of the sex steroid synthesis pathway. The model can simulate the ovarian synthesis and secretion of estrone, estradiol, androstenedione, and testosterone, and their response to endocrine disruption. The model is able to predict ovarian sex steroid concentrations under normal estrous cycle in female rat, and ovarian estradiol concentrations in adult female rats exposed to atrazine, bisphenol A, metabolites of methoxychlor or vinclozolin, and letrozole.
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影响因子：
5.8
作者：
Bois, Frederic Y.
通讯作者：
Bois, Frederic Y.
影响因子：
2.7
作者：
Ishikura, Shuhei;Matsumoto, Kengo;Hara, Akira
通讯作者：
Hara, Akira
DOI：
10.1049/ip-syb:20045033
发表时间：
2005-09-01
期刊：
IEE PROCEEDINGS SYSTEMS BIOLOGY
影响因子：
--
作者：
Liebermeister, W;Klipp, E
通讯作者：
Klipp, E
影响因子：
4.1
作者：
Fang, H;Tong, WD;Sheehan, DM
通讯作者：
Sheehan, DM
影响因子：
3.3
作者：
Holloway, A. C.;Anger, D. A.;Foster, W. G.
通讯作者：
Foster, W. G.