Tissue-selective regulation of androgen-responsive genes.
Tissue-selective regulation of androgen-responsive genes.
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DOI：
10.3109/07435800.2012.668254
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发表时间：
2012
影响因子：
2.1
通讯作者：
Jones JO
中科院分区：
文献类型：
--
作者：
Otto-Duessel M;He M;Jones JO
雄激素调节广泛的生理过程，包括男性性发育，骨骼和肌肉生长，以及行为和认知。由于雄激素在许多组织中起着至关重要的作用，雄激素信号的变化与许多疾病有关。目前还不清楚单一刺激如何实现如此不同的反应。雄激素主要通过雄激素受体（AR）发挥作用，AR是一种在选定的多种组织中表达的激素核受体。为了更好地了解雄激素的组织选择性作用是如何实现的，我们使用以前发表的数据集和我们自己的几个微阵列数据集对微阵列数据进行了比较。这些数据集来源于用全雄激素双氢睾酮（DHT）处理的啮齿动物解剖的临床相关AR表达组织。我们发现，有一个不同的反应，DHT，在每个组织中的雄激素调节基因的重叠很少。基因本体分析还表明，虽然几个组织调节类似的生物过程中响应DHT，雄激素调节的过程是特定的一个或几个组织。因此，似乎雄激素介导的不同生理效应开始时对不同雄激素敏感组织中基因表达的影响差异很大。在这项研究中完成的分析将导致更好地了解雄激素如何介导不同的，组织特异性的过程和更好的方法来评估药物开发过程中AR调节剂的组织选择性作用。
Androgens regulate a wide array of physiological processes, including male sexual development, bone and muscle growth, and behavior and cognition. Because androgens play a vital role in so many tissues, changes in androgen signaling are associated with a plethora of diseases. How such varied responses are achieved by a single stimulus is not well understood. Androgens act primarily through the androgen receptor (AR), a hormone nuclear receptor that is expressed in a select variety of tissues. In order to gain a better understanding of how the tissue-selective effects of androgens are achieved, we performed a comparison of microarray data, using previously published datasets and several of our own microarray datasets. These datasets were derived from clinically relevant, AR-expressing tissues dissected from rodents treated with the full androgen dihydrotestosterone (DHT). We found that there is a diverse response to DHT, with very little overlap of androgen regulated genes in each tissue. Gene ontology analyses also indicated that, while several tissues regulate similar biological processes in response to DHT, most androgen regulated processes are specific to one or a few tissues. Thus, it appears that the disparate physiological effects mediated by androgens begin with widely varying effects on gene expression in different androgen-sensitive tissues. The analysis completed in this study will lead to an improved understanding of how androgens mediate diverse, tissue-specific processes and better ways to assess the tissue-selective effects of AR modulators during drug development.
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影响因子：
3.8
作者：
Gonzalez LO;Corte MD;Vazquez J;Junquera S;Sanchez R;Alvarez AC;Rodriguez JC;Lamelas ML;Vizoso FJ
通讯作者：
Vizoso FJ
影响因子：
16.2
作者：
Shah, NM;Pisapia, DJ;Axel, R
通讯作者：
Axel, R
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5.8
作者：
Sinha-Hikim, I;Taylor, WE;Bhasin, S
通讯作者：
Bhasin, S
影响因子：
4.1
作者：
Brinkmann, AO
通讯作者：
Brinkmann, AO