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

基本信息

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

项目摘要

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

内源性激素和外源性烷基酚化合物对颅内雌激素和雄激素受体（EsR和AnR）表达的影响已在大鼠内侧视前核（MPN）（终纹床核的主核）中进行了免疫组织化学评估。 prBST），内侧杏仁核的后背部分（pdMAmg），被认为与性功能和计算注射媒介油（对照）、17β-雌二醇（E2）、二氢睾酮（DHT）、睾酮（T）、壬基酚（NP）或对叔-的去势大鼠的攻击行为。在对照组中，给予较高剂量的辛基苯酚（OP）后，大脑 EsR 的表达显着增强，而 AnR 的表达在几乎所有大脑区域中几乎完全受到抑制。 E2（100～250 μg/100g，1周）导致prBST和pdMAmg中EsR数量显着减少，AnR数量适度增加，而DHT给药（100.施用较低剂量的 T 后，AnR 的数量显着增加，而 EsR 的数量略有减少（约 250 μg/100g 1 周）。（100-250 μg/100g，持续 1 周）导致 EsR 数量显着减少，特别是在 prBST 和 pdMAmg 中，MPN 的减少要少得多，但在三个给药区域中都没有成功增加 AnR 的数量。在所有三个区域中，较高剂量的 T（1mg/100g，持续 1 周）除了 EsR 显着降低和 AnR 适度增加外，还显着增加 AnR 数量。 NP（40mg/100g，3天）或OP（40mg/100g，3天）被发现在所有三个脑区都显示出雌激素EsR下调作用，如施用较低剂量E2（10～ 25 μg/100g，持续 3 天），这导致 prBST 和 pdMAmg 中的 EsR 数量适度减少，而 MPN 的减少较少。研究强烈表明，除了直接作用于两种受体外，内源性激素和外源性烷基酚化合物还通过上调或下调颅内 EsR 或 AnR 表达来影响脑性组织和激活。 NP 或 OP 等干扰物可以通过对 MPN、prBST 和 pdMAmg 中 EsR 的雌激素下调作用来干扰性别分化以及性功能和攻击行为的调节。