Epidermal Growth Factor Receptor Levels in Reproductive Organs of Female Mice Exposed Neonatally to Diethylstilbestrol

Abstract

Abstract

Binding of epidermal growth factor (EGF) to membrane preparations of vagina, uterus, ovary, oviduct, and liver was examined in mice treated neonatally with diethylstilbestrol (DES) and compared with that in untreated mice. Binding in the vagina (12.5 ± 0.73 fmol/mg protein) was somewhat higher than in the uterus (8.0 ± 0.34 fmol/mg protein). Level of specific binding was of the order: liver (18.4 ± 1.09 and 16.0 ± 1.53 fmol/mg protein) > vagina (12.5 ± 0.73 and 8.2 ± 0.57 fmol/mg protein) > uterus (8.0 ± 0.34 and 6.8 ± 0.56 fmol/mg protein) > ovary (6.8 ± 0.36 and 8.0 ± 1.05 fmol/mg protein) > oviduct (2.1 ± 0.32 and 1.7 ± 0.05 fmol/mg protein) in control and neonatally DES-exposed mice, respectively. Thus, neonatal DES exposure significantly lowered the binding site level only in the vagina, without modifying the binding affinity (K_d = 5.4 × 10^-9 M in controls vs 4.6 × 10^-9 M in DES-exposed mice). Reduction of EGF receptor level in the vagina correlates with ovary-independent persistent proliferation and keratinization of the vagina induced by neonatal DES exposure. EGF receptors were immunohistochemically demonstrated in epithelial cells of vagina, uterus, and oviduct and in stromal cells in uterus and oviduct using a polyclonal antibody to human EGF receptor protein.