CHANGES IN EPIDERMAL GROWTH-FACTOR RECEPTOR AND THE LEVELS OF ITS LIGANDS DURING MENSTRUAL-CYCLE IN HUMAN ENDOMETRIUM

We examined menstrual cycle-dependent changes in the expression of hum an endometrial epidermal growth Deter (EGF), transforming growth facto r alpha (TGF alpha), and epidermal growth factor receptor (EGFR) and t heir mRNA using immunoblot analysis, I-125-EGF binding, and competitiv e reverse transcription and polymerase chain reaction (RT-PCR). We als o studied their localization in the endometrial tissue by immunohistoc hemistry. Endometrial samples were obtained at three stages of menstru ation: the early follicular stage, which exhibits low serum estradiol (E(2)) and progesterone (P) levels; the late follicular stage, which e xhibits high E(2) and low P levels; and the luteal stage, which exhibi ts high E(2) and P levels. Immunohistochemical examination showed that EGF, TGF alpha, and EGFR were localized to the endometrial epithelium . Immunoblot analysis revealed that endometrial EGF, TGF alpha, and EG FR levels were significantly (p < 0.01) increased at the late follicul ar and luteal stages compared to the early follicular stage. I-125-EGF -specific binding levels at the late follicular and luteal stages were significantly (p < 0.01) higher than at the early follicular stage, c onsistent with the results of immunoblot analysis. Competitive RT-PCR revealed that EGF, TGF alpha, and EGFR mRNA levels were significantly (p < 0.01) higher at the late follicular and luteal stages than at the early follicular stage. Changes in EGF, TGF alpha, and EGFR mRNA leve ls were consistent with changes in protein levels. These findings sugg est that synthesis and expression of human endometrial EGF, TGF alpha, and EGFR vary with the stage of the menstrual cycle and that their ex pression in the human endometrium is associated with the increase in t he serum E(2) but not with the increase in P levels.