Retinoic Acid Stimulates 17β-Estradiol and Testosterone Synthesis in Rat Hippocampal Slice Cultures
Retinoic Acid Stimulates 17β-Estradiol and Testosterone Synthesis in Rat Hippocampal Slice Cultures
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DOI：
10.1210/en.2008-1644
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发表时间：
2009-09-01
期刊：
影响因子：
4.8
通讯作者：
Yamazaki, Takeshi
中科院分区：
文献类型：
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作者：
Munetsuna, Eiji;Hojo, Yasushi;Yamazaki, Takeshi
海马体主要参与学习和记忆过程。它的功能受到各种神经调节剂的影响，包括17 β-雌二醇，睾酮和类维生素A。脑合成的类固醇激素作为自分泌和旁分泌调节剂。脑类固醇生成的调节机制尚未完全阐明。视黄酸刺激性腺合成性类固醇。因此，我们研究了视黄酸对大鼠海马雌二醇和睾酮生物合成的影响。我们使用培养的海马切片从10至12日龄的雄性大鼠，以调查从头类固醇。幼年大鼠海马具有类固醇生成酶和类维生素A受体的mRNA。在预培养24小时后使用切片以获得最大的类固醇生成活性，因为培养的切片中的类固醇生成随时间而降低。P450（17 α）、P450芳香化酶和雌激素受体β在切片中的mRNA水平通过9-顺式维甲酸处理而增加，但不通过全反式异构体处理。P450（17 α）mRNA水平的刺激幅度和剂量-反应曲线的形状与细胞类维生素A结合蛋白2型相似，其转录由类维生素A X受体信号激活。9-顺式维甲酸还诱导P450（17 α）蛋白含量增加1.7倍，17 β-雌二醇和睾酮从头合成增加2倍。这些类固醇可以由类固醇前体（例如双烯醇酮或其他类固醇）或由胆固醇合成，作为所谓的神经类固醇。9-顺式维甲酸刺激雌二醇和睾酮合成可能是通过类维生素A X受体信号转导激活P450（17 α）转录引起的。（内分泌学150：4260-4269，2009）
The hippocampus is essentially involved in learning and memory processes. Its functions are affected by various neuromodulators, including 17 beta-estradiol, testosterone, and retinoid. Brain-synthesized steroid hormones act as autocrine and paracrine modulators. The regulatory mechanism underlying brain steroidogenesis has not been fully elucidated. Synthesis of sex steroids in the gonads is stimulated by retinoic acids. Therefore, we examined the effects of retinoic acids on estradiol and testosterone biosynthesis in the rat hippocampus. We used cultured hippocampal slices from 10- to 12-d-old male rats to investigate de novo steroidogenesis. The infant rat hippocampus possesses mRNAs for steroidogenic enzymes and retinoid receptors. Slices were used after 24 h of preculture to obtain maximal steroidogenic activity because steroidogenesis in cultured slices decreases with time. The mRNA levels for P450(17 alpha), P450 aromatase and estrogen receptor-beta in the slices were increased by treatment with 9-cis-retinoic acid but not by all-transisomer. The magnitude of stimulation and the shape of the dose-response curve for the mRNA level for P450(17 alpha) were similar to those for cellular retinoid binding protein type 2, the transcription of which is activated by retinoid X receptor signaling. 9-cis-Retinoic acid also induced a 1.7-fold increase in the protein content of P450(17 alpha) and a 2-fold increase in de novo synthesis of 17 beta-estradiol and testosterone. These steroids may be synthesized from a steroid precursor(s), such as pregnenolone or other steroids, or from cholesterol, as so-called neurosteroids. The stimulation of estradiol and testosterone synthesis by 9-cis-retinoic acid might be caused by activation of P450(17 alpha) transcription via retinoid X receptor signaling. (Endocrinology 150: 4260-4269, 2009)