Effects of exogenous endocrine-disrupters on the brain regions related to sexual differentiation and aggressive behavior

外源性内分泌干扰物对与性别分化和攻击行为相关的大脑区域的影响

• 批准号: 12836010
• 负责人: SHINODA Koh
• 金额: $ 2.37万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12836010/
• 关键词: octylphenol; nonylphenol; endocrine disrupter; sexual differentiation; estrogen receptor; androgen receptor; brain; sex steroid; アロマテース; 内側視索前野; 内側扁桃体; 分界条床核; ビスフェノールA

Effects of endogenous sex-hormones and exogenous alkylphenolic compounds on expression of intracranial estrogen- and androgen-receptor (EsR and AnR) have immunohistochemically been evaluated in the rat medial preoptic nucleus (MPN), principal nucleus of the bed nucleus of the stria terminalis (prBST), posterodorsal part of the medial amygdaloid nucleus (pdMAmg), which have been considered to be related to sexual functions and aggressive behavior. Numbers of the EsRs and AnRs were counted in castrated rats which were injected vehicle-oil (control), 17β-estradiol (E2), dihydrotestosterone (DHT), testosterone (T), nonylphenol (NP) or p-tert-octylphenol (OP). In controls, expression of brain EsRs was strongly enhanced, while that of AnRs was almost completely suppressed in almost all brain regions. Administration of higher dose of E2 (100〜250 μg/100g for 1 week) resulted in prominent decrease of the number of EsR and moderate increase of that of AnR in the prBST and pdMAmg and less increas … More e and decrease in the MPN. Administration of DHT (100〜250 μg/100g 1 week) resulted in prominent increase of that of AnR and slight decrease of the number of EsR in all three regions. Administration of lower dose of T (100〜250 μg/100g for 1 week) resulted in prominent decrease of the number of EsR specifically in the prBST and pdMAmg and far less decrease in the MPN, but not successfully increase that of AnR, in any of the three regions. Administration of higher dose of T (1mg/100g for 1 week) prominently increased the number of the AnR in addition to prominent decrease of EsR have and moderate increase of that of AnR in all three regions. Injection of NP (40mg/100g for 3 days) or OP (40mg/100g for 3 days) was found to show estrogenic EsR-down regulation effects in all three brain regions as seen in the case of administration of lower dose of E2 (10〜25 μg/100g for 3 days), which resulted in moderate decrease of the number of EsR in the prBST and pdMAmg and less decrease in the MPN. Taken together, the present study strongly suggested that endogenous sex-hormone and exogenous alkylphenolic compounds effect on brain sexual organization and activation through up- or down-regulation of intracranial EsR or AnR expression in addition to direct actions on the two receptors. Thus it might be possible that endocrine-disrupters such as NP or OP can interfere sexual differentiation and regulation of the sexual functions and aggressive behavior through their estrogenic down-regulation effects on EsR in the MPN, prBST and pdMAmg. Less

采用免疫组织化学方法评价了内源性性激素和外源性烷基酚类化合物对大鼠内侧视前核（MPN）、终纹床核主核（prBST）、内侧杏仁核后背侧部（pdMAmg）颅内雌激素和雄激素受体（EsR和AnR）表达的影响，这些受体被认为与性功能和攻击行为有关。去势大鼠分别注射溶剂油（对照组）、17β-雌二醇（E2）、双氢睾酮（DHT）、睾酮（T）、壬基酚（NP）和对叔辛基酚（OP），计数雌激素受体（EsRs）和雄激素受体（AnRs）的数量。在对照组中，脑ESRs的表达强烈增强，而AnRs的表达几乎在几乎所有脑区都被完全抑制。高剂量E_2（100 ~ 250 μg/100 g，1周）可使prBST和pdMAmg的EsR明显减少，AnR中度增加，而对PrBST和pdMAmg的AnR增加不明显。 ...更多信息 e和MPN的减少。给药后（100 ~ 250 μg/100 g，1周），三个部位的AnR均显著增加，EsR均略有减少。低剂量T（100 ~ 250 μg/100 g，连续1周）可明显减少PrBST和pdMAmg区的EsR，但对MPN的影响较小，对AnR的影响不明显。高剂量T（1 mg/100 g，连续1周）除使三个区域的EsR显著减少和AnR中度增加外，还使AnR数目显著增加。注射NP（40 mg/100 g，连续3天）或OP（40 mg/100 g，连续3天）均能下调三个脑区的雌激素受体（EsR），与低剂量E_2（10 ~ 25 μg/100 g，连续3天）作用相同，使prBST和pdMAmg区的EsR数目中度减少，而MPN区的EsR数目减少较少。两者合计，本研究强烈建议，内源性激素和外源性烷基酚类化合物的影响，通过上调或下调颅内EsR或AnR的表达，除了直接作用于这两个受体的大脑性组织和激活。因此，内分泌干扰物如NP或OP可能通过其对MPN、prBST和pdMAmg中EsR的雌激素样下调作用来干扰性分化和性功能调节以及攻击行为。少

项目成果

Koumei Takeda: "WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain"Human Molecular Genetics. 10. 477-484 (2001)

Koumei Takeda：“WFS1（沃尔夫拉姆综合征 1）基因产物：培养细胞中内质网的主要亚细胞定位和大鼠脑中的神经元表达”人类分子遗传学。

Shinoda,K.: "Pre-embedding immuno-electron microscopic in the nervous tissues"Histochemistry and Cytochemistry 2001. 117-122 (2001)

Shinoda,K.：“神经组织中的预嵌入免疫电子显微镜”组织化学和细胞化学 2001. 117-122 (2001)

篠田晃: "神経組織における電子顕微鏡を用いた免疫組織化学-プレエンベッディング法-"組織細胞科学2001. 117-122 (2001)

Akira Shinoda：“在神经组织中使用电子显微镜进行免疫组织化学 - 预嵌入方法 -” Histocytochemistry 2001. 117-122 (2001)

Koumei Takeda: "WFS1 (Wolfram syndrome1) gene product : predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain"Human Molecular Genetics. 10・5. 477-484 (2001)

Koumei Takeda：“WFS1（沃尔夫拉姆综合征1）基因产物：培养细胞中内质网的主要亚细胞定位和大鼠脑中的神经表达”人类分子遗传学10・5（2001）。

篠田 晃: "神経組織における電子顕微鏡を用いた免疫組織化学-プレエンベッディング法-"組織細胞科学2001. 117-122 (2001)

Akira Shinoda：“在神经组织中使用电子显微镜进行免疫组织化学 - 预嵌入方法 -” Histocytochemistry 2001. 117-122 (2001)