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成年雄性大鼠脑中芳香化酶mRNA表达的性甾体调节:一项定量非放射性原位杂交研究。

Sex-steroidal regulation of aromatase mRNA expression in adult male rat brain: a quantitative non-radioactive in situ hybridization study.

作者信息

Zhao Changjiu, Fujinaga Ryutaro, Yanai Akie, Kokubu Keiji, Takeshita Yukio, Watanabe Yoshifumi, Shinoda Koh

机构信息

Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.

出版信息

Cell Tissue Res. 2008 Jun;332(3):381-91. doi: 10.1007/s00441-008-0606-8. Epub 2008 Apr 10.

Abstract

Neuronal aromatase, the enzyme that catalyzes the conversion of androgens to estrogens, is involved in brain sexual differentiation, the regulation of reproductive behavior, and gonadotropin secretion. We have previously reported that aromatase P450 (AromP450) protein expression is enhanced by both androgens and estrogens in the principal nucleus of the bed nucleus of the stria terminalis (prBST) and posterodorsal part of the medial amygdaloid nucleus (pdMAm) of the adult rat but is not altered in the central amygdaloid nucleus (CeAm) even after sex-steroid withdrawal or supplementation. Here, we have evaluated, via in situ hybridization with digoxigenin-labeled cRNA probes, the sex-steroidal regulation of brain AromP450 mRNA in the prBST, pdMAm, and CeAm of orchidectomized and adrenalectomized adult male rats treated with sesame oil, testosterone (1 mg/rat/day), dihydrotestosterone (1 mg/rat/day), or 17beta-estradiol (2 microg/rat/day) for 6 days. AromP450-mRNA expression in the prBST and pdMAm was markedly reduced in orchidectomized/adrenalectomized rats treated with sesame oil but strongly enhanced by testosterone or dihydrotestosterone and significantly reinstated by 17beta-estradiol. These results are essentially consistent with those of AromP450 protein expression and thus indicate that enhanced AromP450-protein expression in the prBST and pdMAm reflects transcriptional upregulation and/or post-transcriptional stabilization of its mRNA by sex steroids. In the CeAm, despite moderate AromP450-protein expression, the mRNA has never been detected with or without sex-steroidal manipulations, indicating that the putative sex-steroid-insensitive AromP450 mRNA in the CeAm may be distinct from that in the prBST and pdMAm or, if it occurs at all, expressed at much lower levels.

摘要

神经元芳香化酶是一种催化雄激素转化为雌激素的酶,参与脑性分化、生殖行为调节及促性腺激素分泌。我们之前报道过,成年大鼠终纹床核主核(prBST)和杏仁内侧核后背部(pdMAm)中的芳香化酶P450(AromP450)蛋白表达会受到雄激素和雌激素的增强,但即使在性类固醇撤除或补充后,中央杏仁核(CeAm)中的该蛋白表达也不会改变。在此,我们通过用地高辛标记的cRNA探针进行原位杂交,评估了经去势和肾上腺切除的成年雄性大鼠在分别用芝麻油、睾酮(1mg/大鼠/天)、双氢睾酮(1mg/大鼠/天)或17β-雌二醇(2μg/大鼠/天)处理6天后,prBST、pdMAm和CeAm中脑AromP450 mRNA的性类固醇调节情况。在用芝麻油处理的去势/肾上腺切除大鼠中,prBST和pdMAm中的AromP450-mRNA表达显著降低,但睾酮或双氢睾酮可使其强烈增强,17β-雌二醇也可使其显著恢复。这些结果与AromP450蛋白表达的结果基本一致,因此表明prBST和pdMAm中AromP450蛋白表达的增强反映了其mRNA的转录上调和/或转录后稳定。在CeAm中,尽管有适度的AromP450蛋白表达,但无论有无性类固醇处理均未检测到mRNA,这表明CeAm中假定的对性类固醇不敏感的AromP450 mRNA可能与prBST和pdMAm中的不同,或者即使存在,表达水平也低得多。

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