Connor E E, Meyer M J, Li R W, Van Amburgh M E, Boisclair Y R, Capuco A V
Bovine Functional Genomics Laboratory, USDA, ARS, Beltsville, MD 20705-2350, USA.
J Dairy Sci. 2007 Jun;90 Suppl 1:E55-65. doi: 10.3168/jds.2006-466.
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.
众所周知，雌激素是生长中动物乳腺上皮细胞增殖和导管发育所必需的，而妊娠期的小叶腺泡发育则依赖于孕酮。这些类固醇激素对乳腺中基因表达的影响主要是由它们各自的核激素受体介导的，这些受体作为激素结合转录因子发挥作用。为了深入了解雌激素和孕酮如何调节牛的乳腺生长和功能，我们和其他人已经描述了它们同源核激素受体在牛乳腺整个发育、妊娠和泌乳过程中的表达模式。这项工作已经确定，与啮齿动物的乳腺相比，牛乳腺在泌乳期间缺乏雌激素受体β的表达，而孕酮受体的丰度更高。我们推测，调节孕酮受体表达的雌激素受体亚型之间的相互作用可能导致了这些物种差异。此外，青春期前牛乳腺脂肪垫中大量雌激素受体的表达以及胰岛素样生长因子-I的协同表达表明，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，最近牛基因组序列信息和微阵列技术的可用性使得研究乳腺中对类固醇环境作出反应的全局基因表达成为可能。我们已经鉴定出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、实质中细胞外基质更新增加以及脂肪垫中细胞外基质沉积增加一致。对人类、小鼠和牛乳腺中雌激素反应基因的比较表明，不同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。使用先进分子技术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。
