Role of the transcriptional factors FOXO1 and PPARG on gene expression of SLC2A4 in endometrial tissue from women with polycystic ovary syndrome.
Fifty to seventy percent of patients with polycystic ovary syndrome (PCOS) present hyperinsulinemia. On the other hand, reports indicate that forkhead box class O 1 (FOXO1) and peroxisome proliferator-activated receptor-gamma (PPARG) are involved in the insulin signaling pathway, regulating the gene expression of SLC2A4 (GLUT4). The negative effect of FOXO1 over PPARG transcription disappears when FOXO1 is phosphorylated (p-FOXO1) and excluded from the nucleus, whereas PPARG can suppress gene expression of SLC2A4. Scarce knowledge is available in endometrium of women with PCOS and hyperinsulinemia (PCOSE h-Ins) about the role of these factors. We aimed to evaluate whether the endocrine and metabolic status of PCOS modify the levels of gene and protein expression of FOXO1, PPARG, and SLC2A4 in the endometria from hyperinsulinemic PCOS women compared with controls. In endometria from control (CE, n=7) or PCOSE h-Ins (n=7), we determined the subcellular location and protein levels of p-FOXO1Ser319 and FOXO1/FOXO4 by immunohistochemistry and western blot respectively; gene and/or protein levels of PPARG and SLC2A4 were evaluated by RT-PCR and/or western blot. Cytoplasm location for FOXO1 and p-FOXO1Ser319 was immunodetected in both groups of endometria, showing significantly higher staining in PCOSE h-Ins for these proteins (P<0.05). In PCOSE h-Ins, gene and protein levels of PPARG were significantly higher than in CE, whereas SLC2A4 mRNA was decreased (P<0.05). In conclusion, the derepression of PPARG transcription by the high levels of p-FOXO1Ser319 could partially account for the lower levels of SLC2A4 found in PCOSE h-Ins, suggesting an alteration of the endometrial function in these patients.
Kohan
Karla
K
Laboratory of Endocrinology and Reproductive Biology, University of Chile Clinical Hospital, Santos Dumont # 999, Independencia, Santiago 838-0456, Chile.
Carvajal
Rodrigo
R
Gabler
Fernando
F
Vantman
David
D
Romero
Carmen
C
Vega
Margarita
M
D000328:Adult; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D003593:Cytoplasm / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D051275:Glucose Transporter Type 4 / Q000235:genetics*; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000502:physiology; D047495:PPAR gamma / Q000235:genetics*; D010766:Phosphorylation; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics
D018797:Cell Cycle Proteins; C085126:FOXO1 protein, human; C108803:FOXO4 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D051275:Glucose Transporter Type 4; D007328:Insulin; D047495:PPAR gamma; D012333:RNA, Messenger; C495692:SLC2A4 protein, human; D014157:Transcription Factors