Influence of prenatal exposure to diethylstilbestrol on estrogen and progestin binding proteins in uteri and dimethylbenzanthracene- induced mammary tumors of the rat.

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 micrograms DES during the second (group B) or third (group C) trimester of gestation. Female offspring received 7,12-dimethylbenz[a]anthracene (DMBA) at d 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 found in all mammary tumors assayed. On sucrose gradients of low ionic strength both 8S and 4S forms of the estrogen receptor were identified in mammary tumors, regardless of prenatal treatment. In addition, progestin receptors sedimenting at 4S were identified in these tumors. However, the 7-8S form of the progestin receptor was found only in tumors from intact animals. Levels of progestin receptors were diminished after ovariectomy, both in mammary tumors and in uteri; ovariectomy also 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 third trimester had uterine progestin binding capacities and uterine wet weights that did not decrease proportionally ater ovariectomy. Furthermore, progestin binding capacities in mammary tumors from group C ovariectomized rats were higher than those in the other two groups. In intact rats from group C, cytosol from mammary tumors also had elevated levels of progestin binding; however, no differences in progestin binding were observed in the uteri from these animals. Small differences in estrogen binding capacities in tumor tissues were observed among the three groups; uterine estrogen binding capacities did not vary significantly. Prenatal exposure to DES during the third trimester appeared related to persistent biochemical alterations in rat mammary tumors and uteri; earlier exposure did not have this effect.

[1]  E. Boylan,et al.  Mammary tumorigenesis in the rat following prenatal exposure to diethylstilbestrol and postnatal treatment with 7,12-dimethylbenz[a]anthracene. , 1979, Journal of toxicology and environmental health.

[2]  P. Shubik,et al.  Effects of transplacental exposure to diethylstilbestrol on carcinogenic susceptibility during postnatal life in hamster progeny. , 1979, Cancer research.

[3]  E. Boylan.  Morphological and functional consequences of prenatal exposure to diethylstilbestrol in the rat. , 1978, Biology of reproduction.

[4]  J. Wittliff,et al.  Molecular heterogeneity of cytosolic forms of estrogen receptors from human breast tumors. , 1978, Cancer Research.

[5]  D. Edelman,et al.  In utero exposure to DES. Evaluation and followup of 199 women. , 1978, Obstetrics and Gynecology.

[6]  Edinger Dd.  Screening of DES-exposed women in Rhode Island, 1974-1977. , 1978 .

[7]  Sherman Mr,et al.  Mero-receptors: proteolytic fragments of receptors containing the steroid-binding site. , 1978 .

[8]  J. Wittliff,et al.  Assessment of "activation" of estrogen receptors in lactating mammary gland using DNA-cellulose binding. , 1977, Biochemical and biophysical research communications.

[9]  W. McGuire,et al.  Progesterone and Progesterone Receptors in Experimental Breast Cancer 1 , 2006 .

[10]  S. Robboy,et al.  Age-incidence and risk of diethylstilbestrol-related clear cell adenocarcinoma of the vagina and cervix. , 1977, American journal of obstetrics and gynecology.

[11]  A. Klopper,et al.  Observations on the Variability of Plasma Estriol , 1977, Obstetrics and gynecology.

[12]  T. Nomura,et al.  Induction of urogenital anomalies and some tumors in the progeny of mice receiving diethylstilbestrol during pregnancy. , 1977, Cancer research.

[13]  H. Nagasawa,et al.  Prolactin and murine mammary tumorigenesis: a review. , 1977, Cancer research.

[14]  M. Bibbo,et al.  Follow‐up Study of Male and Female Offspring of DES‐Exposed Mothers , 1977, Obstetrics and gynecology.

[15]  A. Goldman,et al.  Role of testosterone and its metabolites in the differentiation of the mammary gland in rats. , 1976, Endocrinology.

[16]  H. Bern,et al.  Long-term effects of neonatal steroid exposure on mammary gland development and tumorigenesis in mice. , 1976, Journal of the National Cancer Institute.

[17]  E. Desombre,et al.  Estrogen and prolactin receptor concentrations in rat mammary tumors and response to endocrine ablation. , 1976, Cancer research.

[18]  J. Wittliff,et al.  Estrogen receptors and hormone dependency in human breast cancer. , 1976, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[19]  R. Mehta,et al.  Steroid-binding proteins of the mammary gland and their clinical significance in breast cancer. , 1976, Journal of toxicology and environmental health. Supplement.

[20]  R. Warner,et al.  Effects of exposure of neonatal mice to 17beta-estradiol on subsequent age-incidence and morphology of carcinogen-induced mammary dysplasia. , 1975, Journal of the National Cancer Institute.

[21]  H. Bern,et al.  Exposure of neonatal mice to steroids: longterm effects on the mammary gland and other reproductive structures. , 1975, Journal of steroid biochemistry.

[22]  J. Wittliff,et al.  Specific estrogen binding in rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene. , 1975, Cancer research.

[23]  W. McGuire.  [21] Quantitation of estrogen receptor in mammary carcinoma , 1975 .

[24]  J. Wittliff,et al.  Correlations between certain biochemical properties of breast cancer and response to therapy: A preliminary report , 1974 .

[25]  D. Gardner,et al.  Specific estrogen receptors in the lactating mammary gland of the rat. , 1973, Biochemistry.

[26]  J. Raynaud,et al.  Progesterone binding in the immature mouse and rat uterus. , 1973, Steroids.

[27]  W. Wiest,et al.  Progesterone "receptor" in rabbit uterus. I. Characterization and estradiol-17beta augmentation. , 1973, Endocrinology.

[28]  W. Burnett,et al.  Prenatal stilbestrol experience of mothers of young cancer patients , 1973, Cancer.

[29]  B. Henderson,et al.  Stilbestrol and urogenital-tract cancer in adolescents and young adults. , 1973, The New England journal of medicine.

[30]  D. Gardner,et al.  Specific estrogen-receptors in the neoplastic and lactating mammary gland of the rat. , 1972, Biochemical and biophysical research communications.

[31]  J. Barlow,et al.  Clear‐cell adenocarcinoma (“mesonephroma”) of the vagina. Three cases associated with maternal synthetic nonsteroid estrogen therapy , 1972 .

[32]  E. Jensen,et al.  Estrogen receptors and breast cancer response to adrenalectomy. , 1971, National Cancer Institute monograph.

[33]  W. McGuire,et al.  Comparison of macromolecular binding of estradiol in hormone-dependent and hormone-independent rat mammary carcinoma. , 1971, Cancer research.

[34]  J. Gorski,et al.  Control of estrogen binding protein concentration under basal conditions and after estrogen administration. , 1971, Biochemistry.

[35]  E. Baulieu,et al.  Progesterone in uterus and plasma. I. Binding in rat uterus 105,000 g supernatant. , 1970, Endocrinology.

[36]  R. Scully,et al.  Adenocarcinoma of the vagina in adolescence. A report of 7 cases including 6 clear‐cell carcinomas (so‐called mesonephromas) , 1970 .

[37]  Takao Mori.  Changes in Reproductive Organs and Some Other Glands in Old C3H/MS Mice Treated Neonatally with Low Doses of Estrogen , 1968 .

[38]  E. Jensen,et al.  A two-step mechanism for the interaction of estradiol with rat uterus. , 1968, Proceedings of the National Academy of Sciences of the United States of America.

[39]  S. Korenman.  Radio-ligand binding assay of specific estrogens using a soluble uterine macromolecule. , 1968, The Journal of clinical endocrinology and metabolism.

[40]  J. Gorski,et al.  Hormone receptors: studies on the interaction of estrogen with the uterus. , 1968, Recent progress in hormone research.

[41]  E. Jensen,et al.  Estrogen-binding substances of target tissues. , 1969, Science.

[42]  K. Hoshino,et al.  Development and growth of mammary glands of mice prenatally exposed to estradiol benzoate. Abstr. , 1967 .

[43]  K. Hoshino.  Development and growth of mammary glands of cba mice prenatally exposed to progesterone. Abstr. , 1966 .

[44]  W. J. Waddell,et al.  A simple ultraviolet spectrophotometric method for the determination of protein. , 1956, The Journal of laboratory and clinical medicine.

[45]  G. Scatchard,et al.  THE ATTRACTIONS OF PROTEINS FOR SMALL MOLECULES AND IONS , 1949 .

[46]  A. Ivy,et al.  Experimental intersexuality. The effects of estrogens on the antenatal sexual development of the rat , 1940 .

[47]  A. Ivy,et al.  Experimental intersexuality. The paradoxical effects of estrogens on the sexual development of the female rat , 1939 .

[48]  A. Ivy,et al.  Experimental Intersexuality , 1939 .

[49]  R. Robinson,et al.  Œstrogenic Activity of Certain Synthetic Compounds , 1938, Nature.