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

内源性性激素和外源性烷基酚类化合物对大鼠内视前核（MPN）、终纹床核主核（prBST）、内侧杏仁核（pdMAmg）后鼻侧部分颅内雌激素和雄激素受体（EsR和AnR）表达的影响进行了免疫组织化学研究，这些受体被认为与性功能和攻击行为有关。对去势大鼠分别注射车辆油（对照）、17β-雌二醇（E2）、二氢睾酮（DHT）、睾酮(T)、壬基酚（NP）和对叔辛基酚（OP），计数esr和anr的数量。在对照组中，脑内esr的表达被强烈增强，而anr的表达在几乎所有脑区几乎完全被抑制。大剂量E2 （100 ~ 250 μg/100g，连续1周）可使大鼠prBST和pdmag中EsR数量显著减少，AnR数量适度增加，MPN的增加较少，增加较多，减少。给予DHT （100 ~ 250 μg/100g 1周）后，3个区域的AnR显著增加，EsR数量略有减少。低剂量T （100 ~ 250 μg/100g，持续1周）导致prBST和pdMAmg的EsR数量明显减少，MPN的减少幅度较小，但AnR的增加没有成功。高剂量T （1mg/100g，连续1周）显著增加了AnR的数量，并显著降低了EsR的数量，AnR的数量在三个区域均有适度增加。与低剂量E2 （10 ~ 25 μg/100g，连续3天）组相比，NP （40mg/100g，连续3天）或OP （40mg/100g，连续3天）组在大鼠脑内三个脑区均表现出雌激素性EsR下调的作用，导致prBST和pdmag中EsR数量适度减少，MPN减少较少。综上所述，本研究强烈提示，内源性性激素和外源性烷基酚类化合物除了直接作用于两种受体外，还通过上调或下调颅内EsR或AnR的表达来影响脑组织的组织和激活。因此，NP或OP等内分泌干扰物可能通过其对MPN、prBST和pdMAmg中EsR的雌激素下调作用，干扰性别分化和对性功能和攻击行为的调节。少

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