Involvement of calcium and calmodulin in the regulation of ovarian steroidogenesis in Atlantic croaker (Micropogonias undulatus) and modulation by Aroclor 1254

Involvement of calcium and calmodulin in the regulation of ovarian steroidogenesis in Atlantic croaker (Micropogonias undulatus) and modulation by Aroclor 1254
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DOI:
10.1016/j.ygcen.2005.06.005
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发表时间:
2005-12-01
影响因子:
2.7
通讯作者:
Thomas, P
Thomas, P
中科院分区:
医学3区
文献类型:
--
作者:
Benninghoff, AD;Thomas, P

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研究了钙依赖性信号转导通路在大西洋花鱼卵巢类固醇生成调控中的作用。钙离子载体A23187和离子霉素处理可使体外培养的黄花鱼卵巢组织基础类固醇蓄积增加2 ~ 5倍。A23187增强人绒毛膜促性腺激素(hCG)诱导的睾酮(T)积累,而抑制雌二醇-17 β (E2)的积累和T到E的转化,表明细胞内钙调节芳香酶活性。在EGTA和电压敏感钙通道(VSCCs)和肌醇-1,4,5-三磷酸受体(IP(3)Rs)抑制剂的存在下,促性腺激素对卵巢甾体生成的刺激减弱,表明细胞内和细胞外储存的钙释放是促性腺激素启动的信号转导途径的组成部分。由于钙调素抑制剂W-7和三氟拉嗪(TFP)减弱了hcg刺激的T和E的积累,钙调素也参与了黄花鱼卵巢类固醇生成的调节。这些结果与之前在金鱼中报道的结果大致相似,并表明四足动物中涉及促性腺激素刺激卵巢类固醇生成的主要钙依赖信号通路也存在于硬骨鱼中。此外,首次在脊椎动物卵巢中证实了钙参与芳香酶活性的调节。最后,急性暴露于0.001-1 ppm的Aroclor 1254可诱导hcg刺激的E2积累增加5倍,并且通过与VSCCs抑制剂和钙调素抑制剂共同处理可减弱这种效应,这表明环境污染物存在一种新的内分泌干扰机制,涉及调节类固醇生成的钙依赖信号通路的改变。(c) 2005爱思唯尔公司版权所有。
The involvement of calcium-dependent signal transduction pathways in the regulation of ovarian steroidogenesis was investigated in Atlantic croaker. Treatment with the calcium ionophores A23187 and ionomycin caused a 2- to 5-fold increase in basal steroid accumulation by croaker ovarian tissue in vitro. A23187 potentiated human chorionic gonadotropin (hCG)-induced testosterone (T) accumulation, whereas it inhibited accumulation of estradiol-17 beta (E2) and the conversion of T to E, suggesting that intracellular calcium modulates aromatase enzyme activity. Gonadotropin stimulation of ovarian steroidogenesis was decreased in the presence of EGTA and inhibitors of voltage-sensitive calcium channels (VSCCs) and inositol-1,4,5-triphosphate-receptors (IP(3)Rs), indicating that releases of calcium from both intracellular and extracellular stores are components of the signal transduction pathways initiated by gonadotropin. Calmodulin is also involved in the regulation of ovarian steroidogenesis in croaker, since the calmodulin inhibitors W-7 and trifluoperazine (TFP) attenuated hCG-stimulated T and E, accumulation. These results are broadly similar to those reported previously in goldfish and suggest that the major calcium-dependent signaling pathways involved in gona-dotropin stimulation of ovarian steroidogenesis in tetrapods are also present in teleosts. In addition, the involvement of calcium in the regulation of aromatase activity was demonstrated for the first time in a vertebrate ovary. Finally, acute exposure to 0.001-1 ppm Aroclor 1254 induced up to a 5-fold increase in hCG-stimulated E2 accumulation, and this effect was attenuated by co-treatment with inhibitors of VSCCs and calmodulin, suggesting the existence of a novel mechanism of endocrine disruption by an environmental contaminant involving alteration of calcium-dependent signaling pathways regulating steroidogenesis. (c) 2005 Elsevier Inc. All rights reserved.