Regulation of epidermal growth factor receptor synthesis by ovarian steroids in human endometrial cells in culture

The aim of this study was to investigate the effect of oestradiol and progesterone on epidermal growth factor (EGF) binding in human endometrial glands and stromal cells in culture. Monolayers of isolated glands or stromal cells were cultured for 6 days in the presence or absence of steroids which were replenished daily. Binding of 125I-labelled EGF was measured in the presence and absence of unlabelled EGF. Over a 6 day period, oestradiol caused a dose-dependent increase in the number of EGF receptors in stromal cells, with a maximum effect of 150% control at a concentration of 10 nmol l-1. The effect of progesterone was also dose dependent and reached a maximum of 170% control at 100 nmol progesterone l-1. Oestradiol and progesterone in combination caused a greater increase in EGF receptor concentration than did either steroid alone (control, 100 +/- 11%; oestradiol, 144 +/- 11% control; progesterone, 200 +/- 20% control; oestradiol and progesterone, 288 +/- 6% control). Steroid treatment did not alter the affinity of the receptor for EGF. The stage of the cycle of the tissue did not affect the response to steroids. The effect of oestradiol was inhibited by the anti-oestrogen ICI182780, and that of progesterone by the anti-progestin RU486. In endometrial glands, neither oestradiol nor progesterone affected the number of EGF receptors, but the two steroids in combination induced an increase of 140 +/- 23% control where control was 100 +/- 15%. These data demonstrate that oestradiol and progesterone increase the number of EGF receptors in vitro, and suggest that EGF is involved in mediating the actions of these steroids on the processes of proliferation and differentiation in the human endometrium.