Regulation of gene expression in the bovine mammary gland by ovarian steroids
Regulation of gene expression in the bovine mammary gland by ovarian steroids
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DOI：
10.3168/jds.2006-466
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发表时间：
2007-01-01
影响因子：
3.5
通讯作者：
Capuco, A. V.
中科院分区：
文献类型：
--
作者：
Connor, E. E.;Meyer, M. J.;Capuco, A. V.
众所周知，雌激素是生长期动物乳腺上皮细胞增殖和导管发育所必需的，妊娠期小叶肺泡发育依赖于孕酮。这些类固醇激素对乳腺中基因表达的影响主要由其各自的核激素受体介导，其作为与乳腺结合的转录因子发挥作用。为了深入了解雌激素和孕激素如何调节牛乳腺的生长和功能，我们和其他人已经表征了在整个发育、妊娠和泌乳过程中牛乳腺中其同源核激素受体的表达模式。这项工作已经确定了一个缺乏表达的雌激素受体β和更丰富的孕激素受体在哺乳期的牛乳腺，与啮齿动物的腺体。我们推测调节孕激素受体表达的雌激素受体亚型之间的相互作用可能有助于这些物种差异。此外，在青春期前的牛乳房脂肪垫中，雌激素受体的大量表达，沿着协调的胰岛素样生长因子-I的表达，表明该组织可能通过雌激素反应性旁分泌机制刺激实质生长。此外，最近可用的牛基因组序列信息和微阵列技术，允许全球基因表达的研究在乳腺类固醇环境的反应。我们已经鉴定了100多个雌激素反应基因，其中大多数是新的雌激素基因靶点。雌激素诱导的基因表达变化与乳腺上皮细胞增殖增加、实质细胞外基质周转增加和脂肪垫细胞外基质沉积增加一致。人类、小鼠和牛乳腺中雌激素反应基因的比较表明，物种之间存在相当大的差异，以及常见雌激素受体基因靶点中调控元件的潜在差异。利用先进的分子生物学技术进行的持续研究应该有助于阐明转录水平上乳腺功能的复杂调节。
It is well established that estrogen is required for mammary epithelial cell proliferation and ductal development in the growing animal, and that lobuloalveolar development during gestation is dependent on progesterone. The effects of these steroid hormones on gene expression in the mammary gland are mediated primarily by their respective nuclear hormone receptors, which function as hormone-bound transcription factors. To gain insight into how estrogen and progesterone regulate mammary gland growth and function in cattle, we and others have characterized the expression patterns of their cognate nuclear hormone receptors in the bovine mammary gland throughout development, pregnancy, and lactation. This work has identified a lack of expression of estrogen receptor beta and a greater abundance of progesterone receptor during lactation in the bovine mammary gland, compared with the rodent gland. We speculate that interactions among the estrogen receptor isoforms that regulate progesterone receptor expression may contribute to these species differences. Further, demonstrated expression of substantial quantities of estrogen receptor within the prepubertal bovine mammary fat pad, along with coordinated insulin-like growth factor-I expression, suggests that this tissue may stimulate parenchymal growth via an estrogen-responsive paracrine mechanism. In addition, the recent availability of bovine genomic sequence information and microarray technologies has permitted the study of global gene expression in the mammary gland in response to the steroid environment. We have identified more than 100 estrogen-responsive genes, of which the majority are novel estrogen gene targets. Estrogen-induced changes in gene expression were consistent with increased mammary epithelial cell proliferation, increased extracellular matrix turnover in parenchyma, and increased extracellular matrix deposition in the fat pad. A comparison of estrogen-responsive genes in the mammary glands of humans, mice, and cattle suggests considerable variation among species, as well as potential differences in regulatory elements in common estrogen receptor gene targets. Continuing studies using advanced molecular techniques should assist in elucidating the complex regulation of mammary function at the transcript level.