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

本研究以化学方法观察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）和杏仁内侧核后背侧部（pdMAmg）脑内雌激素受体（EsR）和雄激素受体（AnR）表达的影响。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

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