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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

用免疫组织化学方法研究了内源性性激素和外源性烷基酚类化合物对大鼠视前内侧核(Mpn)、终纹床核主核(PrBst)、杏仁内侧核背侧部(PdMAmg)等与性功能和攻击行为有关的脑区内雌雄激素受体(ESR和ANR)表达的影响。给去势大鼠注射车油(对照组)、17β-雌二醇(E_2)、双氢睾酮(DHT)、睾酮(T)、壬基酚(NP)和对叔辛基酚(OP)，计算ESRS和ANRs的数目。在对照组中，脑内ESRS的表达显著增强，而AnRs的表达几乎在几乎所有脑区都被完全抑制。大剂量雌二醇(10 0~2 5 0μg/10 0 g，共1周)可使大鼠血沉显著减少，血沉中度升高，…增加较少MPN增加，MPN减少。给予DHT100~250μg/100g，1周后，3个脑区的ANR显著升高，血沉数量略有减少。小剂量T(10 0~2 5 0μg/10 0 g，共1周)可使上述3个区域的血沉明显减少，但不能有效地增加ANR，但对MPN的影响较小。给予大剂量T(1 mg/100g，1周)后，除血沉显著降低外，ANR数显著增加，三区ANR数均有中度增加。注射NP(40 mg/100g，连用3天)或OP(40 mg/100g，连用3天)在三个脑区均表现出雌激素样的血沉下调作用，与小剂量E_2(10~25μ，g/100g，连用3天)的作用相同，导致pRBST和pdMAmg内的血沉数目中度减少，而MPN的减少较小。综上所述，本研究有力地表明，内源性性激素和外源性烷基酚类化合物除了直接作用于这两种受体外，还通过上调或下调脑内ESR或ANR的表达来影响脑性组织和激活。因此，内分泌干扰物如NP或OP可能通过对MPN、prBST和pdMAmg中ESR的雌激素下调作用而干预性分化、性功能和攻击行为的调节。较少