Binding and retention of estrogen in the uterus of hamsters treated neonatally with diethylstilbestrol

Abstract

We have shown previously that postpubertal estrogen exposure promotes the development of uterine tumors in hamsters treated neonatally with diethylstilbestrol (DES). The purpose of this study was to determine if the uterine estrogen receptor system of adult hamsters was altered after neonatal DES treatment. There was no effect on the concentration, subcellular distribution, apparent binding affinity, sedimentation properties, surface charge characteristics or ligand specificity of uterine estrogen receptor in ovariectomized, estrogen-replaced animals. Furthermore, neonatal DES treatment had no effect on the subcellular distribution of radioactivity in the uterus of adult animals ovariectomized 1 week before challenge with [ 3H]-estradiol-17β(E 2). However, the amount of radioactivity taken up and specifically bound within the uterus 6 h after [ 3H]-E 2 challenge was less in DES-treated compared to control animals. Six hours after challenge with unlabeled E 2, the concentration (pmol/g tissue) of occupied but not total nuclear estrogen receptor was reduced in DES-treated animals. The difference in uterine radioactivity levels and occupied nuclear receptor retention appears to be due to a difference in estrogen metabolism since the systemic concentration of authentic [ 3H]-E 2 was lower in DES-treated animals compared to control. These results demonstrate no DES-induced change in the physicochemical or functional properties of the uterine estrogen receptor system, suggesting that a lesion in this receptor system is not involved in the etiology of uterine tumor development following neonatal DES exposure. However, the DES-treated animal appears to have an enhanced estrogen metabolism.