Novel genes regulated by gonadotropins in granulosa cells: new perspectives on their physiological functions
Novel genes regulated by gonadotropins in granulosa cells: new perspectives on their physiological functions
复制标题
DOI：
10.1016/s0303-7207(03)00074-1
复制
发表时间：
2003-04-28
影响因子：
4.1
通讯作者：
Amsterdam, A
中科院分区：
文献类型：
--
作者：
Amsterdam, A
卵泡刺激素（FSH）是由垂体分泌的一种重要激素，通过与颗粒细胞上的特异性受体相互作用，控制卵泡内卵母细胞的发育。其生物活性包括刺激细胞间通讯和上调类固醇生成，但受FSH调控的整个基因谱尚未完全表征。我们已经建立了大鼠和人FSH反应性颗粒细胞系，其表达FSH受体的速率比原代细胞高20倍。由于这些细胞系是单克隆的，因此预计它们在整个细胞群中具有均一的RNA组成，这增加了产生FSH调节基因的独特视图的可能性，消除了其他细胞类型污染的可能性。使用Affyssin DNA微阵列来发现新的FSH调控基因，我们发现了以前没有报道过的FSH调控的基因。这些包括编码以下的基因：（1）蛋白酶;（2）生长因子和细胞因子;（3）参与细胞间通讯和与神经系统连接的蛋白质;（4）蛋白磷酸酶和激酶;（5）抗氧化剂和抗毒物;（6）G偶联蛋白。这些结果有助于我们进一步了解FSH在刺激卵泡细胞发育、调节卵巢细胞内和细胞间通讯以及选择优势卵泡过程中的作用机制。当人类颗粒细胞，从体外受精患者中获得的暴露于hLH或hFSH刺激和这些细胞的mRNA进行了分析，通过DNA微阵列，新的基因，类似于那些发现的FSH调节FSH反应细胞系，被发现在人类原代细胞。这表明，在我们的实验室建立的永生化细胞系统可以作为一个有用的系统，扩大频谱的真实基因调节促性腺激素刺激正常卵巢功能和卵巢功能障碍。(C)2003爱思唯尔科学爱尔兰有限公司保留所有权利。
Follicular stimulating hormone (FSH) is a key hormone secreted from the pituitary, which controls the development of the follicle-enclosed oocytes in the mammalian ovary by interacting with specific receptors located exclusively on granulosa cells. Its biological activity involves stimulation of intercellular communication and upregulation of steroidogenesis, yet the entire spectrum of genes which are regulated by FSH are not fully characterized. We have established rat and human FSH responsive granulosa cell lines, which express FSH receptors at 20-times higher rates compared to primary cells. Since the lines are monoclonal, they are expected to have a homogeneous composition of RNA among the entire cell population, which increases the probability of yielding a distinct view of genes modulated by FSH eliminating the possibility of other cell types contamination. Using Affymetrix DNA microarrays to uncover novel FSH-regulated genes, we discovered genes not reported earlier to be regulated by FSH. These include genes coding for (1) proteases; (2) growth factors and cytokines; (3) proteins involved in intercellular communication and connection with the nervous system; (4) protein phosphatases and kinases; (5) anti oxidants and anti-toxicants; (6) G-coupled proteins. These findings can deepen our understanding in the mechanism of FSH action in stimulation of the development of the ovarian follicular cells, in the modulation of ovarian intracellular and intercellular communication and in the process of selection of the dominant follicle. When human granulosa cells, obtained from in vitro fertilization patients were exposed to either hLH- or hFSH stimulation and mRNAs of these cells were analyzed by DNA microarrays, novel genes, similar to those found modulated by FSH in FSH responsive cell lines, were discovered in the human primary cells. This suggests that the immortalized cell systems established in our laboratory could serve as a useful system expanding the spectrum of authentic genes modulated by gonadotropin stimulation in normal ovarian function and in ovarian malfunction. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.