Androgen Action in the Epididymis
Androgen Action in the Epididymis
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DOI：
10.2164/jandrol.111.014266
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发表时间：
2011-11-01
影响因子：
--
通讯作者：
Hamzeh, Mahsa
中科院分区：
文献类型：
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作者：
Robaire, Bernard;Hamzeh, Mahsa
雄激素负责维持附睾的结构和功能。然而，很少有人知道雄激素的作用是如何介导的，以及雄激素剥夺后附睾细胞的完整性恢复的机制。我们首先提供了一个概述，什么是已知的雄激素在这个组织中的作用，然后在雄激素剥夺条件下，雄激素在改变细胞结构和功能的初始和顺序的作用，目前的数据。使用形态学分析和大鼠模型，我们确定了上皮细胞高度和管腔直径的变化，以及在不同区域和雄激素戒断和替代后的不同时间点增殖细胞的数量。在雄激素剥夺组织中发生的基因激活或抑制的序列在睾酮、双氢睾酮（DHT）和雌二醇的2种活性代谢物的再给药后进行检查。虽然很少有基因受到雌二醇的调控，但许多基因受到DHT的影响。表皮生长因子（EGF）和胰岛素样生长因子-1（IGF 1）似乎在DHT激活的早期反应途径中起重要作用，因为它们在调节许多其他基因的表达中起作用。利用PC-1附睾细胞系研究了参与介导雄激素恢复附睾上皮细胞完整性作用的细胞内信号通路。IGF 1和EGF受体被发现是雄激素受体介导的MAPK/ERK途径激活的重要介质。总之，这些研究提供了一个更好的了解雄激素的作用机制，在附睾。
Androgens are responsible for maintaining epididymal structure and functions. However, little is known about how androgen action is mediated and the mechanisms underlying the restoration of the integrity of epididymal cells after androgen deprivation. We first provide an overview of what is known about androgen action in this tissue and then present data on the initial and sequential roles of androgens in altering cellular architecture and function in an androgen-deprived condition. Using morphometric analysis and the rat model, we identified changes in epithelial cell height and lumen diameter, as well as in the numbers of proliferating cells in different regions and at various time points after androgen withdrawal and replacement. The sequence of gene activation or suppression that occurred in the androgen-deprived tissue was examined upon the readministration of the 2 active metabolites of testosterone, dihydrotestosterone (DHT) and estradiol. Although few genes were regulated by estradiol, many were affected by DHT. Epidermal growth factor (EGF) and insulinlike growth factor-1 (IGF1) appear to play an important role in the early response pathway activated by DHT because of their function in the regulation of the expression of many other genes. The intracellular signaling pathway involved in mediating the action of androgen in restoring epididymal epithelial cell integrity was investigated using the PC-1 epididymal cell line. IGF1 and EGF receptors were found to be important mediators of androgen receptor mediated activation of the MAPK/ERK pathways. Together, these studies provide a greater understanding of the mechanisms of androgen action in the epididymis.