Vienonen Annika, Miettinen Susanna, Bläuer Merja, Martikainen Paula M, Tomás Eija, Heinonen Pentti K, Ylikomi Timo
Department of Cell Biology, Medical School, University of Tampere, Tampere, Finland.
J Soc Gynecol Investig. 2004 Feb;11(2):104-12. doi: 10.1016/j.jsgi.2003.09.003.
To study the expression of nuclear receptors and cofactors in human endometrium and myometrium in proliferative and secretory phases of the menstrual cycle.
Multiprobe ribonuclease protection assay and real-time reverse transcriptase polymerase chain reaction were used to quantitate mRNA levels of steroid receptors, vitamin D receptor (VDR), retinoic acid receptors (RAR), and cofactors AIB1 (amplified in breast cancer-1), CBP (cyclic adenosine monophosphate response element binding protein), pCAF (p300/CBP-associated factor), TIF2 (transcription intermediary factor-2), N-CoR (nuclear receptor corepressor), and SMRT (silencing mediator of repressed transcription). Cyclin A expression was analyzed to determine the proliferation status of the tissues.
The expression of androgen receptor, estrogen receptors alpha and beta, progesterone receptor, and RARalpha followed cyclin A expression. There was more abundant expression in the proliferative phase endometrium than in the secretory phase endometrium. Glucocorticoid receptor, VDR, RARbeta, and RARgamma were stably expressed during the menstrual cycle in both endometrium and myometrium. Cofactors N-CoR, SMRT, pCAF, CBP, TIF2, AIB1, and p300 mRNAs were expressed in all samples in both endometrium and myometrium. N-CoR, pCAF, AIB1, and p300 appeared not to be regulated when comparing proliferative and secretory phases of the cycle. Individual differences were found in the expression levels of both nuclear receptors and cofactors.
The menstrual cycle-dependent regulation of nuclear receptor expression was more apparent in the endometrium than in the myometrium, whereas cofactor expression was not cycle dependent. There were individual differences in the expression levels of different receptors and cofactors. In hormonal therapy these differences might result in different responses, depending on the patient as well as the ligand used.
研究核受体及其辅因子在月经周期增殖期和分泌期人子宫内膜及子宫肌层中的表达。
采用多探针核糖核酸酶保护分析法及实时逆转录聚合酶链反应,对甾体受体、维生素D受体(VDR)、视黄酸受体(RAR)以及辅因子AIB1(乳腺癌扩增基因1)、CBP(环磷酸腺苷反应元件结合蛋白)、pCAF(p300/CBP相关因子)、TIF2(转录中介因子2)、N-CoR(核受体共抑制因子)和SMRT(转录沉默中介因子)的mRNA水平进行定量分析。分析细胞周期蛋白A的表达,以确定组织的增殖状态。
雄激素受体、雌激素受体α和β、孕激素受体及RARα的表达随细胞周期蛋白A的表达而变化。增殖期子宫内膜中的表达比分泌期子宫内膜更为丰富。糖皮质激素受体、VDR、RARβ和RARγ在月经周期中于子宫内膜和子宫肌层均稳定表达。辅因子N-CoR、SMRT、pCAF、CBP、TIF2、AIB1和p300的mRNA在子宫内膜和子宫肌层的所有样本中均有表达。比较月经周期的增殖期和分泌期时,N-CoR、pCAF、AIB1和p300似乎不受调控。核受体和辅因子的表达水平存在个体差异。
核受体表达的月经周期依赖性调控在子宫内膜中比在子宫肌层中更为明显,而辅因子表达不依赖于月经周期。不同受体和辅因子的表达水平存在个体差异。在激素治疗中,这些差异可能导致不同的反应,这取决于患者以及所使用的配体。