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Expression of Nuclear Receptors and Cofacotrs in Human Endometrium and Myometrium

Department of Cell Biology, Medical School, University of Tampere; Departments of Pathology, Obstetrics and Gynecology and Clinical Chemistry, Tampere University Hospital, Tampere, Finalnd; Annika.Vienonen{at}uta.fi

Susanna Miettinen, MS

Merja Bläuer, PhD

Paula M. Martikainen, MD, PhD

Eija Tomás, MD, PhD

Pentti K. Heinonen, MD, PhD

Timo Ylikomi, MD, PhD

Department of Cell Biology, Medical School, University of Tampere; Departments of Pathology, Obstetrics and Gynecology and Clinical Chemistry, Tampere University Hospital, Tampere, Finalnd

Objective: To study the expression of nuclear receptors and cofactors in human endometrium and myometrium in proliferative and secretory phases of the menstrual cycle.

Methods: 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.

Results: The expression of androgen receptor, estrogen receptors and ß, progesterone receptor, and RAR followed cyclin A expression. There was more abundant expression in the proliferative phase endometrium than in the secretory phase endometrium. Glucocorticoid receptor, VDR, RARß, and RAR 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.

Conclusion: The menstrual cycle-dependent regulation of nuclear receptor expression was more apparent in the endometrium that in the myometrium, whereas cofactor expression was 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.

Key Words: Steroid receptor • vitamin D receptor • retinoic acid receptor • cofactor • uterus

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