Genomics of estradiol-3-sulfate action in the ovine fetal hypothalamus.
Genomics of estradiol-3-sulfate action in the ovine fetal hypothalamus.
复制标题
DOI：
10.1152/physiolgenomics.00127.2011
复制
发表时间：
2012-07
影响因子：
4.6
通讯作者：
M. Rabaglino;E. Richards;N. Denslow;M. Keller‐Wood;C. Wood
中科院分区：
文献类型：
--
作者：
M. Rabaglino;E. Richards;N. Denslow;M. Keller‐Wood;C. Wood
在妊娠晚期的胎羊中，血浆中的磺基结合雌激素浓度比非结合雌激素高40-100倍。本研究的目的是确定雌二醇-3-硫酸酯（E（2）S）在羊胎脑中作用的基因组学。假设是E（2）S刺激参与神经内分泌通路的基因，这些通路在妊娠末期指导或促进胎儿发育。研究了四组长期插管的绵羊双胎（胎龄：妊娠120-127天），其中一组脑室内输注E（2）S（1 mg/天），另一组未输注（对照）。安乐死后，从胎脑中提取mRNA样品。鉴于下丘脑-垂体-肾上腺轴控制中该脑区的重要功能，本研究仅采用下丘脑样本。按照Agilent方案对设计用于绵羊的单色8 × 15微阵列进行微阵列分析。共有363个已知基因在E（2）S处理后显着上调（P < 0.05）。使用Cytoscape/Bingo软件进行网络和富集分析，并通过定量实时PCR验证结果。从这个分析中得到的主要的过度代表的生物过程是摄食行为，缺氧反应，和转化生长因子信号。值得注意的是，与摄食行为有关的基因（神经肽Y和刺豚鼠相关蛋白）受到E（2）S处理的诱导最强烈。总之，E（2）S可能是激活羔羊接近出生后生活的食欲，缺氧反应和神经保护途径的机制的重要组成部分。
In fetal sheep during late gestation sulfoconjugated estrogens in plasma reach a concentration 40-100 times greater than unconjugated estrogens. The objective of the present study was to determine the genomics of estradiol-3-sulfate (E(2)S) action in the ovine fetal brain. The hypothesis was that E(2)S stimulates genes involved in the neuroendocrine pathways that direct or facilitate fetal development at the end of gestation. Four sets of chronically catheterized ovine twin fetuses were studied (gestational age: 120-127 days gestation) with one infused with E(2)S intracerebroventricularly (1 mg/day) and the other remaining untreated (control). After euthanasia, mRNA samples were extracted from fetal brains. Only hypothalamic samples were employed for this study given the important function of this brain region in the control of the hypothalamus-pituitary-adrenal axis. Microarray analysis was performed following the Agilent protocol for one-color 8 × 15 microarrays, designed for Ovis aries. A total of 363 known genes were significantly upregulated by the E(2)S treatment (P < 0.05). Network and enrichment analyses were performed using the Cytoscape/Bingo software, and the results validated by quantitative real-time PCR. The main overrepresented biological processes resulting from this analysis were feeding behavior, hypoxia response, and transforming growth factor signaling. Notably, the genes involved in the feeding behavior (neuropeptide Y and agouti-related protein) were the most strongly induced by the E(2)S treatment. In conclusion, E(2)S may be an important component of the mechanism for activating orexigenic, hypoxia responsiveness and neuroprotective pathways in the lamb as it approaches postnatal life.