Regulation of epidermal growth factor and insulin-like growth factor I receptors by estradiol and progesterone in normal and neoplastic endometrial cell cultures

Growth factors are polypeptides which regulate cell proliferation through binding to specific receptor proteins. Normal and neoplastic human endometrium have been shown to express epidermal growth factor (EGF) and insulin-like growth factor I (IGF-1) receptors. Endometrial cell cultures were used to test modulation of EGF and IGF-1 receptors in response to steroid hormones. Endometrial gland and stroma cells were separated by enzymatic dispersion and were incubated in medium containing estradiol (10, 100, or 1000 pg/ml) or progesterone (1, 10, or 100 ng/ml) followed by radioligand assays. Normal endometrial cultures ( n = 6) treated with estradiol demonstrated 40% less EGF binding than control cultures ( P < 0.05), while IGF-1 binding was unaffected. Stromal cells treated identically decreased in only one treatment group. Progesterone treatment stimulated a significant increase in EGF and IGF-1 receptors in gland cultures. Cultures derived from adenocarcinoma ( n = 2) demonstrated decreased EGF binding compared with normal endometrium ( P < 0.05). Carcinoma cells treated with progesterone resulted in a dose-dependent increase in EGF binding over control ( P < 0.05). These data illustrate effects of steroid hormones upon growth factor receptors in human endometrium, and suggest involvement of growth factors in the regulation of normal and neoplastic endometrial growth.