Activity and expression of steroidogenic enzymes in the brain of adult zebrafish
Activity and expression of steroidogenic enzymes in the brain of adult zebrafish
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DOI：
10.1111/j.1460-9568.2011.07731.x
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发表时间：
2011-07-01
影响因子：
3.4
通讯作者：
Kah, Olivier
中科院分区：
文献类型：
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作者：
Diotel, Nicolas;Do Rego, Jean-Luc;Kah, Olivier
成年硬骨鱼的大脑表现出一些独特而有趣的特征，特别是与作为神经前体的放射状神经胶质细胞的持续存在有关的强烈的神经发生活动，以及由Cyp19a1b基因的强烈表达支持的高芳香化酶活性。值得注意的是，Cyp19a1b的表达仅限于放射状胶质细胞，这表明雌激素能够调节它们的活动。这就提出了可用于芳构化的C19雄激素的中心或外围来源的问题。本研究旨在研究成年斑马鱼脑内其他主要类固醇生成酶的活性和表达。我们通过高效液相色谱证明斑马鱼脑具有将[(3)H]-孕烯醇酮转化为多种放射性标记类固醇的能力，如17OH-孕烯醇酮、脱氢表雄酮、雄烯二酮、睾酮、二氢睾酮、雌酮、雌二醇、孕酮以及二氢和四氢孕酮。接下来，我们通过原位杂交表明，关键类固醇生成酶的信使，如Cyp11a1(P450(SCC))、3β-HSD、CyP17和Cyp19a1b在前脑广泛表达，它们表现出总体相似的模式。结合芳香酶B免疫组织化学和原位杂交，我们发现在芳香酶B阳性的放射状突起中有部分Cyp11a1、3β-hsd和CYP17信使，提示有mRNA输出。这组结果首次证明，鱼的大脑可以产生真正的神经类固醇，可能是在放射状胶质细胞中。鉴于放射状胶质细胞在鱼类的整个生命周期中都是脑干细胞，我们认为至少其中一些神经类固醇与持续的神经发生过程有关。
The brain of adult teleost fish exhibits several unique and interesting features, notably an intense neurogenic activity linked to persistence of radial glial cells acting as neural progenitors, and a high aromatase activity supported by strong expression of the cyp19a1b gene. Strikingly, cyp19a1b expression is restricted to radial glial cells, suggesting that estrogens are able to modulate their activity. This raises the question of the origin, central or peripheral, of C19 androgens available for aromatization. This study aimed to investigate the activity and expression of other main steroidogenic enzymes in the brain of adult zebrafish. We demonstrate by high-performance liquid chromatography that the zebrafish brain has the ability to convert [(3)H]-pregnenolone into a variety of radiolabeled steroids such as 17OH-pregnenolone, dehydroepiandrosterone, androstenedione, testosterone, dihydro-testosterone, estrone, estradiol, progesterone, and dihydro-and tetrahydro-progesterone. Next, we show by in situ hybridization that messengers for key steroidogenic enzymes, such as Cyp11a1 (P450(SCC)), 3 beta-Hsd, Cyp17 and Cyp19a1b, are widely expressed in the forebrain where they exhibit an overall similar pattern. By combining aromatase B immunohistochemistry with in situ hybridization, we show that cyp11a1, 3 beta-hsd and cyp17 messengers are found in part in aromatase B-positive radial processes, suggesting mRNA export. This set of results provides the first demonstration that the brain of fish can produce true neurosteroids, possibly in radial glial cells. Given that radial glial cells are brain stem cells during the entire lifespan of fish, it is suggested that at least some of these neurosteroids are implicated in the persisting neurogenic process.