Estrogen induces expression of endometrial epidermal growth factor receptors before implantation

Pharmacological doses of 17 beta-estradiol increase epidermal growth factor binding to uterine membranes.

To determine whether physiological elevated E2 concentrations in the preimplantation phase of rabbits and preovulatory phase of women cause epidermal growth factor (EGF) receptor expression, we performed radioligand binding studies of endometrial membranes with [125I]-EGF.

Unmated rabbits revealed a binding maximum (Bmax) of 514 +/- 197 fmol/mg protein for [125I]-EGF. The Bmax values increased significantly to 1424 +/- 430 fmol/mg on day 1 and to 2244 +/- 224 fmol/mg on day 2 after mating. On day 3 the Bmax values decreased to 1409 +/- 238 fmol/mg and on days 4 to 8 the binding maxima were not significantly different from the Bmax values of unmated rabbits. In ovariectomized rabbits a significant increase of [125I]-EGF-binding could be mimicked 12 and 18 h after the intramuscular injection of estradiol (40 micrograms/kg). The estradiol-induced increase of [125I]-EGF Bmax values was blocked by the parallel application of the antiestrogen tamoxifen. Progesterone (2 mg/kg) did not influence [125I]-EGF-binding to endometrial membranes. Membrane preparations of the human endometrium from the periovulatory phase bound significantly more [125I]-EGF compared to endometrium of the early proliferative phase. The expression of EGF receptor mRNA was localized in the epithelial cells of the human endometrium by in situ hybridization technique.

These results provide insight into the regulation of the autocrine and paracrine factor EGF in the endometrium during the preimplantation period.