Influence of prenatal exposure to diethylstilbestrol on estrogen and progestin binding proteins in uteri and d1methylbenzanthracene‐induced mammary tumors of the rat

Publisher Website
Google Scholar
Abstract
Various characteristics of steroid binding proteins from mammary tumors and uteri of rats exposed prenatally to diethylstilbestrol (DES) were examined. Pregnant rats were treated with no hormone (group A) or with a total dose of 1.2 .mu.g DES during the 2nd (group B) or 3rd (group C) trimester of gestation. Female offspring received 7,12-dimethylbenz[a]anthracene at day 50 .+-. 1. Animals with large mammary tumors were subjected to bilateral ovariectomy. Seven months after carcinogen treatment, the experiment was terminated. High-affinity binding sites for [3H]estradiol-17.beta. and [3H]R5020 were present in all mammary tumors assayed. On sucrose gradients of low ionic strength, 8S and 4S forms of the estrogen receptor were identified in mammary tumors, regardless of prenatal treatment. Progestin receptors sedimenting at 4S were identified in these tumors. The 7-8S form of the progestin receptor occurred only in tumors from intact animals. Levels of progestin receptors were diminished after ovariectomy, in mammary tumors and in uteri; ovariectomy resulted in a significant reduction in uterine wet weight in the hormone exposure groups, as expected. Unlike groups A and B, rats exposed to DES during the 3rd trimester had uterine progestin binding capacities and uterine wet weights that did not decrease proportionally after ovariectomy. Progestin binding capacities in mammary tumors from group C ovariectomized rats were higher than those in the other 2 groups. In intact rats from group C, cytosol from mammary tumors had elevated levels of progestin binding; however, no differences in progestin binding occurred in the uteri from these animals. Small differences in estrogen binding capacities in tumor tissues occurred among the 3 groups; uterine estrogen binding capacities did not vary significantly. Prenatal exposure to DES during the 3rd trimester appeared related to persistent biochemical alterations in rat mammary tumors and uteri; earlier exposure did not have this effect.