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

内源性激素和外源烷基苯酚化合物对颅内雌激素和雄激素受体（ESR和ANR）表达的影响在大鼠培养基前核（MPN）中评估了免疫组织化学的影响。（PDMAMG），被认为与性功能和侵略性行为有关。将ESR和ANR的数量计数在cast割的大鼠中计数，这些大鼠被注入载体油（对照），17β-雌二醇（E2），二氢睾丸激素（DHT），睾丸激素（T），Nonylphenol（NP）或P-TERT-TERT-TERT-辛基 - 辛基苯酚（OP）。在对照中，大脑ESR的表达得到了强烈的增强，而在几乎所有大脑区域中，ANR的表达几乎都被完全抑制。施用较高剂量的E2（1周持续1周）导致ESR数量的显着减少，而PRBST和PDMAMG中ANR的数量中度增加，而MPN的E越来越少。 DHT的给药（100-250μg/100g 1周）导致ANR的明显减少，并且在所有三个区域中的ESR数量略有减少。较低剂量的T（100-250μg/100g持续1周）导致PRBST和PDMAMG中ESR的数量显着减少，而MPN的降低却降低了，但在三个区域中的任何一个地区都没有成功增加ANR。除了ESR的显着降低，在所有三个地区，ANR的显着降低和ANR的中等增加，较高剂量的T（1周16周）占据了ANR的数量显着增加。在所有三个大脑区域中，发现NP（40mg/100g持续3天）或OP（40mg/100g 3天）在所有三个大脑区域中显示出雌激素ESR向下调节效应，如施用较低剂量的E2（10-25μg/100g）（10-25μg/100g 3天），导致ESR和PDM的较少降低，导致了ESR和PDM的中等减少。综上所述，本研究强烈建议内源性性激素和外源性烷基苯酚化合物对脑性组织的影响以及通过上调或下调颅内ESR或ANR表达，除了对两个受体的直接作用外。 NP或OP等内分泌疾病可能会通过对MPN，PRBST和PDMAMG中ESR的影响来干扰性功能的性别分化和调节性能以及攻击行为。较少的