Identification of Early Response Genes and Pathway Activated by Androgens in the Initial Segment and Caput Regions of the Regressed Rat Epididymis
Identification of Early Response Genes and Pathway Activated by Androgens in the Initial Segment and Caput Regions of the Regressed Rat Epididymis
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DOI：
10.1210/en.2010-0023
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发表时间：
2010-09-01
期刊：
影响因子：
4.8
通讯作者：
Robaire, Bernard
中科院分区：
文献类型：
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作者：
Hamzeh, Mahsa;Robaire, Bernard
为了确定雄激素和雌激素在睾丸切除后的退化附睾中的初始反应，我们测定了睾酮的两种代谢物——5 -二氢睾酮（DHT）或17 -雌二醇（E2）——在退化的大鼠附睾中引发的基因表达变化。切除成年大鼠的睾丸，8 d后分别植入空植入物（对照）、dht填充植入物或e2填充植入物。分别于12 h、1 d和7 d处死大鼠，提取RNA并在Rat230-2.0 Affymetrix阵列上检测。在早期时间点确定对DHT或E2有反应的探针组；虽然一些人的表达受到抑制，但其他许多人的表达要么是短暂的，要么是长期的升高。神经生长因子受体（Ngfr）和S100钙结合蛋白G （S100g）是在12 h检测到E2上调的两个基因。在DHT早期表现出显著反应的基因中，内皮素1 （Edn1）、骨形态发生蛋白4 （Bmp4）和IGF结合蛋白3 （Igfbp3）被抑制，IGF- i （Igf1）被诱导。根据生物学功能对DHT上调或下调基因进行分类。使用PathwayStudio 4.0，我们确定了相互关联并直接影响彼此表达或调节的基因。表皮生长因子和igf - 1因其调控和表达许多其他基因的功能而在该通路中发挥重要作用。这些结果为雄激素作用对对附睾功能重要的基因表达的影响提供了新的见解。（中华医学会精神病学分会，2010）
To identify the initial response to androgens and estrogens in the orchidectomized, regressed epididymis, we determined the gene expression changes triggered by the administration of either of two metabolites of testosterone, 5 alpha-dihydrotestosterone (DHT) or 17 beta-estradiol (E2), in the regressed rat epididymis. Adult rats were orchidectomized and 8 d later implanted with either empty implants (control), DHT-filled-, or E2-filled-polydioxanone implants. Rats were euthanized 12 h, 1 d, and 7 d later, and RNA was extracted and probed on Rat230-2.0 Affymetrix arrays. Probe sets that respond to DHT or E2 were identified at early time points; although the expression of some was repressed, the expression of many others was either transiently or chronically elevated. Nerve growth factor receptor (Ngfr) and S100 calcium binding protein G (S100g) were two E2 up-regulated genes detected at 12 h. Among the genes that showed a dramatic early response to DHT were endothelin 1 (Edn1), bone morphogenetic protein 4 (Bmp4), and IGF binding protein 3 (Igfbp3), which were suppressed, and IGF-I (Igf1), which was induced. Genes that were up-or down-regulated by DHT were classified based on biological function. Using PathwayStudio 4.0, we identified genes that were linked and directly influenced either the expression or regulation of one another. Epidermal growth factor and IGF-I play an important role in the pathway due to their function in regulation and expression of many other genes. These results provide novel insights into the impact of androgen action on the expression of genes that are important for epididymal function. (Endocrinology 151: 4504-4514, 2010)