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Female Reproductive Tract |
a Departments of Obstetrics and Gynecology,
b Physiology and Biophysics,
and
c Medicine, University of Illinois at Chicago College of Medicine and VA Chicago Healthcare System (West Side), Chicago, Illinois 60612
d Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520
e CNRS UMR 8542, Ecole Normale Superieure, Paris, France
Insulin-like growth factor binding protein-1 (IGFBP-1) is abundantly expressed in the liver and decidualized endometrium. FKHR, a FOXO forkhead transcription factor, stimulates IGFBP-1 promoter activity in liver cells through the insulin response sequences (IRSs). HOXA10, a homeobox transcription factor, is important in the decidualization process. Here we show that FKHR and HOXA10 are expressed in baboon endometrium during the menstrual cycle and pregnancy. Levels are lowest during the follicular phase and highest in pregnancy. Reporter gene studies reveal that FKHR stimulates both baboon and human IGFBP-1 promoter activity, whereas HOXA10 alone has a relatively weak effect. When FKHR and HOXA10 are expressed together, promoter activity is markedly up-regulated, which is indicative of cooperativity. A DNA binding-deficient FKHR mutant fails to stimulate promoter activity, even in the presence of HOXA10, and deletion or mutation of IRSs also disrupts the effect of FKHR and cooperativity with HOXA10. Conversely, the IRS region placed upstream of the 31 base pair IGFBP-1 minimal promoter is sufficient to mediate effects of FKHR and cooperativity with HOXA10. Pull-down studies reveal physical association between GST-FKHR and 35S-HOXA10. These studies show that FKHR and HOXA10 interact directly and can function cooperatively to stimulate IGFBP-1 promoter activity in endometrial cells and perhaps in other settings.
2 Correspondence: Asgerally T. Fazleabas, Department of Obstetrics and Gynecology, University of Illinois at Chicago, 820 South Wood Street, M/C 808, Chicago, IL 60612. FAX: 312 996 4238; asgi{at}uic.edu
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