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

Sex-steroidal regulation of aromatase mRNA expression in adult male rat brain: a quantitative non-radioactive in situ hybridization study
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DOI:
10.1007/s00441-008-0606-8
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发表时间:
2008-04
影响因子:
3.6
通讯作者:
Changjiu Zhao;Ryutaro Fujinaga;Akie Yanai;K. Kokubu;Y. Takeshita;Yoshifumi Watanabe;K. Shinoda
Changjiu Zhao;Ryutaro Fujinaga;Akie Yanai;K. Kokubu;Y. Takeshita;Yoshifumi Watanabe;K. Shinoda
中科院分区:
生物学3区
文献类型:
--
作者:
Changjiu Zhao;Ryutaro Fujinaga;Akie Yanai;K. Kokubu;Y. Takeshita;Yoshifumi Watanabe;K. Shinoda

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神经元芳香化酶是一种催化雄激素向雌激素转化的酶,它参与大脑的性别分化、生殖行为的调节和促性腺激素的分泌。我们之前报道过雄性激素和雌性激素在成年大鼠终纹床核主核(prBST)和内侧杏仁核(pdam)的后嗅侧部分增强芳香化酶P450 (aromatase P450)蛋白的表达,但在中央杏仁核(CeAm)中,即使在停用或补充性类固醇后也不会改变。在这里,我们通过地高辛标记的cRNA探针原位杂交,评估了性激素对去兰科和去肾上腺的成年雄性大鼠的prBST、pdMAm和CeAm中AromP450 mRNA的调节作用,这些大鼠分别用香油、睾酮(1 mg/大鼠/天)、二氢睾酮(1 mg/大鼠/天)或17β-雌二醇(2 μg/大鼠/天)治疗6天。香油处理的去兰/去肾上腺大鼠prBST和pdmm中AromP450-mRNA的表达明显降低,而睾酮或二氢睾酮则显著增强,17β-雌二醇则显著恢复。这些结果与AromP450蛋白表达的结果基本一致,因此表明prBST和pdam中AromP450蛋白表达的增强反映了性类固醇对其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,但无论是否使用性类固醇操作,都从未检测到该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pdam中的不同,或者如果存在的话,其表达水平要低得多。
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 17β-estradiol (2 μg/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 17β-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.