Tokumoto Toshinobu, Tokumoto Mika, Nagahama Yoshitaka
Department of Biology and Geosciences, Faculty of Science, National University Corporation Shizuoka University, Shizuoka 422-8529, Japan.
Reprod Biol Endocrinol. 2005 Dec 9;3:69. doi: 10.1186/1477-7827-3-69.
Oocyte maturation in lower vertebrates is triggered by maturation-inducing hormone (MIH), which acts on unidentified receptors on the oocyte surface and induces the activation of maturation-promoting factor (MPF) in the oocyte cytoplasm. We previously described the induction of oocyte maturation in fish by an endocrine-disrupting chemical (EDC), diethylstilbestrol (DES), a nonsteroidal estrogen.
In this study, stimulatory and inhibitory effects of EDCs and natural steroids on oocyte maturation were examined in zebrafish. For effective agents, some details about the mechanism in induction or inhibition of maturation were examined. Possible groups of DES interacting with the MIH receptor are discussed based on relative potency of steroids to induce maturation.
Among agents tested, tamoxifen (TAM) and its metabolite 4-hydroxytamoxifen (4-OHT) showed stimulatory activity similar to DES. The time courses of the change in germinal vesicle breakdown and an intracellular molecular event (the synthesis of cyclin B) induced by TAM were indistinguishable from those induced by MIH. In contrast, pentachlorophenol (PCP) had a potent inhibitory effect on MIH-induced oocyte maturation. PCP inhibited not only MIH-induced maturation but also DES- and TAM-induced maturation. Methoxychlor also inhibited maturation when oocytes were pre-treated with this agent.
These results suggest that EDCs act as agonists or antagonists in the induction of oocyte maturation in fish.
低等脊椎动物的卵母细胞成熟由成熟诱导激素（MIH）触发，MIH作用于卵母细胞表面未明确的受体，并诱导卵母细胞胞质中成熟促进因子（MPF）的激活。我们之前描述了一种内分泌干扰化学物质（EDC）——己烯雌酚（DES），一种非甾体雌激素，可诱导鱼类卵母细胞成熟。
在本研究中，检测了EDC和天然类固醇对斑马鱼卵母细胞成熟的刺激和抑制作用。对于有效药物，研究了其诱导或抑制成熟机制的一些细节。基于类固醇诱导成熟的相对效力，讨论了DES与MIH受体相互作用的可能基团。
在所测试的药物中，他莫昔芬（TAM）及其代谢产物4-羟基他莫昔芬（4-OHT）显示出与DES相似的刺激活性。TAM诱导的生发泡破裂变化的时间进程以及细胞内分子事件（细胞周期蛋白B的合成）与MIH诱导的无法区分。相比之下，五氯苯酚（PCP）对MIH诱导的卵母细胞成熟具有强大的抑制作用。PCP不仅抑制MIH诱导的成熟，还抑制DES和TAM诱导的成熟。当卵母细胞用甲氧滴滴涕预处理时，甲氧滴滴涕也抑制成熟。
这些结果表明，EDC在鱼类卵母细胞成熟诱导中起激动剂或拮抗剂的作用。
