Shyamala G, Schneider W, Schott D
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
Endocrinology. 1990 Jun;126(6):2882-9. doi: 10.1210/endo-126-6-2882.
Previously we have shown that in normal murine mammary glands progesterone receptor (PgR) levels are modulated as a function of development and differentiation such that lactating mammary glands do not contain detectable levels of PgR as measured by steroid binding. The objective of the present study was to determine whether the lack of steroid binding in lactating mammary glands was due to the absence of receptor protein and if so whether it was accompanied by an alternation in the pattern of PgR gene expression. Accordingly, we have performed an immunological analysis of murine mammary PgR isolated from different developmental states and have also examined these tissues for PgR gene expression. In mammary tissues from all developmental states other than lactation, immunoreactive PgR corresponding to both A and B forms of the protein were detected. Analysis for PgR mRNA revealed multiple species in mammary tissues and the relative order of abundance of the various transcripts and their sizes were approximately 6.9 greater than 8.7 greater than 3.5 greater than 2.7 greater than 4.2. The 6.9 and 8.7 kilobase transcripts accounted for between 70-80% of total mRNA. All five species of mRNA were detected in tissues from nulliparous mice which decreased dramatically during pregnancy, became undetectable during lactation, and were once again detectable in tissues from mice undergoing lactational involution. Experiments designed specifically to examine the effect of estradiol on mammary PgR mRNA revealed that in contrast to tissues from other developmental states, lactating mammary glands were unable to respond to estradiol with an increase in PgR mRNA. Based on these findings and the fact that estrogenic insensitivity of lactating mammary glands coexists with the presence of ER we propose that in this tissue there is an alteration in the estrogen dependent transcriptional regulation of PgR gene expression.
先前我们已经表明，在正常的小鼠乳腺中，孕酮受体（PgR）水平会随着发育和分化而受到调节，以至于通过类固醇结合测量发现，泌乳期乳腺中不存在可检测到的PgR水平。本研究的目的是确定泌乳期乳腺中缺乏类固醇结合是否是由于受体蛋白的缺失，如果是，那么其是否伴随着PgR基因表达模式的改变。因此，我们对从不同发育状态分离出的小鼠乳腺PgR进行了免疫分析，并且还检测了这些组织中的PgR基因表达。在除泌乳期外的所有发育状态的乳腺组织中，均检测到了与该蛋白的A和B两种形式相对应的免疫反应性PgR。对PgR mRNA的分析显示，乳腺组织中有多种mRNA，各种转录本的相对丰度顺序及其大小约为6.9kb＞8.7kb＞3.5kb＞2.7kb＞4.2kb。6.9kb和8.7kb的转录本占总mRNA的70%-80%。在未孕小鼠的组织中检测到了所有这五种mRNA，在怀孕期间其数量急剧减少，在泌乳期变得无法检测到，而在处于泌乳期退化的小鼠组织中又再次可以检测到。专门设计用于检测雌二醇对乳腺PgR mRNA影响的实验表明，与其他发育状态的组织不同，泌乳期乳腺无法通过增加PgR mRNA来对雌二醇作出反应。基于这些发现以及泌乳期乳腺对雌激素不敏感与雌激素受体（ER）的存在并存这一事实，我们提出，在该组织中，PgR基因表达的雌激素依赖性转录调节发生了改变。
