Expression of nuclear receptors and cofactors in human endometrium and myometrium.
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 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.


CONCLUSIONS
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.
Vienonen
Annika
A
Department of Cell Biology, Medical School, University of Tampere, Tampere, Finland. Annika.Vienonen@uta.fi
Miettinen
Susanna
S
Bläuer
Merja
M
Martikainen
Paula M
PM
Tomás
Eija
E
Heinonen
Pentti K
PK
Ylikomi
Timo
T
D000123:Acetyltransferases / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D019925:Cyclin A / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004717:Endometrium / Q000737:chemistry*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D015870:Gene Expression; D051548:Histone Acetyltransferases; D006801:Humans; D008597:Menstrual Cycle; D009215:Myometrium / Q000737:chemistry*; D009687:Nuclear Proteins / Q000235:genetics; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D051958:Nuclear Receptor Coactivator 2; D056921:Nuclear Receptor Coactivator 3; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D019925:Cyclin A; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D051958:Nuclear Receptor Coactivator 2; D056921:Nuclear Receptor Coactivator 3; D012333:RNA, Messenger; D011944:Receptors, Androgen; D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C498001:NCOA2 protein, human; C539127:NCOR1 protein, human; C539130:NCOR2 protein, human