Alkylphenol xenoestrogens with varying carbon chain lengths differentially and potently activate signaling and functional responses in GH3/B6/F10 somatomammotropes.
Alkylphenol xenoestrogens with varying carbon chain lengths differentially and potently activate signaling and functional responses in GH3/B6/F10 somatomammotropes.
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DOI：
10.1289/ehp.0800182
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发表时间：
2009-05
影响因子：
10.4
通讯作者：
Watson CS
中科院分区：
文献类型：
--
作者：
Kochukov MY;Jeng YJ;Watson CS
侧链长度不同的烷基苯酚[乙基苯酚、丙基苯酚、辛基苯酚和壬基苯酚（分别为EP、PP、OP和NP）]和双酚A（BPA）代表了一大组结构相关的具有内分泌破坏作用的异种雌激素。它们的快速非基因组效应依赖于细胞信号传导的结构和由此产生的功能是未知的。我们在膜雌激素受体-α富集的GH 3/B6/F10垂体瘤细胞中比较了烷基酚与BPA和17β-雌二醇（E2）的非基因组雌激素活性。这些作用包括钙（Ca）信号传导、催乳素（PRL）释放、细胞外调节激酶（ERK）磷酸化和细胞增殖。我们使用Fura-2对Ca进行成像，通过放射免疫测定法测量PRL释放，通过固定细胞免疫测定法检测ERK磷酸化，并使用结晶紫测定法估计细胞数量。所有化合物引起的钙振荡频率和细胞内钙体积在100 fM至1 nM浓度的增加，虽然长链烷基酚是最有效的。所有雌激素引起快速PRL释放的浓度低至1 fM至10 pM; EP，PP和NP的效力超过E2。所有化合物在1 nM时均产生ERK磷酸化的类似增加，在2.5-5 min时产生快速峰，随后是失活和额外的60 min峰（BPA除外）。E2、BPA和PP在5分钟时ERK激活的剂量-反应模式相似，而EP引起更大的效应。只有E2和NP增加细胞数。一些快速的雌激素反应与雌激素分子的疏水性相关;疏水性越强的OP和NP在Ca和细胞增殖反应方面表现得越上级，而疏水性越弱的EP和PP在ERK激活方面表现得越好。烷基酚是有效的雌激素，在唤起这些非基因组的反应，有助于复杂的功能，它们的疏水性可以在很大程度上预测这些行为。
Alkylphenols varying in their side-chain lengths [ethyl-, propyl-, octyl-, and nonylphenol (EP, PP, OP, and NP, respectively)] and bisphenol A (BPA) represent a large group of structurally related xenoestrogens that have endocrine-disruptive effects. Their rapid nongenomic effects that depend on structure for cell signaling and resulting functions are unknown. We compared nongenomic estrogenic activities of alkylphenols with BPA and 17β-estradiol (E2) in membrane estrogen receptor-α–enriched GH3/B6/F10 pituitary tumor cells. These actions included calcium (Ca) signaling, prolactin (PRL) release, extracellular-regulated kinase (ERK) phosphorylation, and cell proliferation. We imaged Ca using fura-2, measured PRL release via radioimmunoassay, detected ERK phosphorylation by fixed cell immunoassay, and estimated cell number using the crystal violet assay. All compounds caused increases in Ca oscillation frequency and intracellular Ca volume at 100 fM to 1 nM concentrations, although long-chain alkylphenols were most effective. All estrogens caused rapid PRL release at concentrations as low as 1 fM to 10 pM; the potency of EP, PP, and NP exceeded that of E2. All compounds at 1 nM produced similar increases in ERK phosphorylation, causing rapid peaks at 2.5–5 min, followed by inactivation and additional 60-min peaks (except for BPA). Dose–response patterns of ERK activation at 5 min were similar for E2, BPA, and PP, whereas EP caused larger effects. Only E2 and NP increased cell number. Some rapid estrogenic responses showed correlations with the hydrophobicity of estrogenic molecules; the more hydrophobic OP and NP were superior at Ca and cell proliferation responses, whereas the less hydrophobic EP and PP were better at ERK activations. Alkylphenols are potent estrogens in evoking these nongenomic responses contributing to complex functions; their hydrophobicity can largely predict these behaviors.
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影响因子：
8.8
作者：
Gallard, H;Leclercq, A;Croué, JP
通讯作者：
Croué, JP
影响因子：
10.4
作者：
Calafat AM;Kuklenyik Z;Reidy JA;Caudill SP;Ekong J;Needham LL
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Needham LL
影响因子：
2.7
作者：
Bulayeva, NN;Gametchu, B;Watson, CS
通讯作者：
Watson, CS
影响因子：
4.4
作者：
BURBACK, BL;PERRY, JJ
通讯作者：
PERRY, JJ
影响因子：
2.4
作者：
de Jager, C;Bornman, MS;van der Horst, G
通讯作者：
van der Horst, G