In vitro binding of insulin and epidermal growth factor to human endometrium and endocervix

Abstract

The distribution of receptors for insulin and epidermal growth factor along the longitudinal axis of the uterine cavity was studied in 28 uteri obtained from women of reproductive age undergoing hysterectomy for benign conditions. Insulin binding to crude plasma membranes was higher (p < 0.05) in the secretory than in the proliferative phase of the menstrual cycle in all uterine segments (fundus to cervix). Epidermal growth factor binding did not change during the menstrual cycle but the number of epidermal growth factor binding sites was higher in the cervix than in the fundus (p < 0.05). Scatchard plots of binding data, obtained with crude plasma membranes from pooled uteri, were curvilinear; the high-affinity sites had dissociation constants of 1 to 4 nmol/L and receptor concentrations of 100 to 300 fmol/mg of protein, for both iodine 125-labeled insulin and 125I-labeled epidermal growth factor. In plasma membranes, obtained from another 15 uteri, mouse nerve growth factor (3.3 μg/ml) decreased the binding of insulin by an average of 17% (p < 0.005); in the decidua of a pregnant uterus at 12 weeks Scatchard analysis showed that nerve growth factor decreased the affinity but not the number of insulin-binding sites. Nerve growth factor had no effect on epidermal growth factor binding. Human prolactin (2 μg/ml) also decreased insulin binding by an average of 18% (n = 5, p < 0.025) but had no effect on epidermal growth factor binding. These “baseline” data will be useful in further studies of the possible interactions between (1) receptors for various peptide growth factors and (2) sex steroid hormones, in normal and neoplastic endometrium and cervix.