Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Jul 23;93(15):8112–8116. doi: 10.1073/pnas.93.15.8112

Genetic separation of tumor growth and hemorrhagic phenotypes in an estrogen-induced tumor.

D L Wendell 1, A Herman 1, J Gorski 1
PMCID: PMC38884  PMID: 8755612

Abstract

Chronic administration of estrogen to the Fischer 344 (F344) rat induces growth of large, hemorrhagic pituitary tumors. Ten weeks of diethylstilbestrol (DES) treatment caused female F344 rat pituitaries to grow to an average of 109.2 +/- 6.3 mg (mean +/- SE) versus 11.3 +/- 1.4 mg for untreated rats, and to become highly hemorrhagic. The same DES treatment produced no significant growth (8.9 +/- 0.5 mg for treated females versus 8.7 +/- 1.1 for untreated females) or morphological changes in Brown Norway (BN) rat pituitaries. An F1 hybrid of F344 and BN exhibited significant pituitary growth after 10 weeks of DES treatment with an average mass of 26.3 +/- 0.7 mg compared with 8.6 +/- 0.9 mg for untreated rats. Surprisingly, the F1 hybrid tumors were not hemorrhagic and had hemoglobin content and outward appearance identical to that of BN. Expression of both growth and morphological changes is due to multiple genes. However, while DES-induced pituitary growth exhibited quantitative, additive inheritance, the hemorrhagic phenotype exhibited recessive, epistatic inheritance. Only 5 of the 160 F2 pituitaries exhibited the hemorrhagic phenotype; 36 of the 160 F2 pituitaries were in the F344 range of mass, but 31 of these were not hemorrhagic, indicating that the hemorrhagic phenotype is not merely a consequence of extensive growth. The hemorrhagic F2 pituitaries were all among the most massive, indicating that some of the genes regulate both phenotypes.

Full text

PDF
8112

Images in this article

8114Fig. 1
on p.8114

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. CLIFTON K. H., MEYER R. K. Mechanism of anterior pituitary tumor induction by estrogen. Anat Rec. 1956 May;125(1):65–81. doi: 10.1002/ar.1091250106. [DOI] [PubMed] [Google Scholar]
  3. De Nicola A. F., von Lawzewitsch I., Kaplan S. E., Libertun C. Biochemical and ultrastructural studies on estrogen-induced pituitary tumors in F344 rats. J Natl Cancer Inst. 1978 Sep;61(3):753–763. [PubMed] [Google Scholar]
  4. Elias K. A., Weiner R. I. Direct arterial vascularization of estrogen-induced prolactin-secreting anterior pituitary tumors. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4549–4553. doi: 10.1073/pnas.81.14.4549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Holtzman S., Stone J. P., Shellabarger C. J. Influence of diethylstilbestrol treatment on prolactin cells of female ACI and Sprague-Dawley rats. Cancer Res. 1979 Mar;39(3):779–784. [PubMed] [Google Scholar]
  6. Kohn E. C., Liotta L. A. Molecular insights into cancer invasion: strategies for prevention and intervention. Cancer Res. 1995 May 1;55(9):1856–1862. [PubMed] [Google Scholar]
  7. Lande R. The minimum number of genes contributing to quantitative variation between and within populations. Genetics. 1981 Nov-Dec;99(3-4):541–553. doi: 10.1093/genetics/99.3-4.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Liotta L. A., Steeg P. S., Stetler-Stevenson W. G. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell. 1991 Jan 25;64(2):327–336. doi: 10.1016/0092-8674(91)90642-c. [DOI] [PubMed] [Google Scholar]
  9. Lloyd R. V. Estrogen-induced hyperplasia and neoplasia in the rat anterior pituitary gland. An immunohistochemical study. Am J Pathol. 1983 Nov;113(2):198–206. [PMC free article] [PubMed] [Google Scholar]
  10. Lloyd R. V., Landefeld T. D. Detection of prolactin messenger RNA in rat anterior pituitary by in situ hybridization. Am J Pathol. 1986 Oct;125(1):35–44. [PMC free article] [PubMed] [Google Scholar]
  11. Lloyd R. V., Mailloux J. Effects of diethylstilbestrol and propylthiouracil on the rat pituitary. An immunohistochemical and ultrastructural study. J Natl Cancer Inst. 1987 Oct;79(4):865–873. [PubMed] [Google Scholar]
  12. Marx J. How cells cycle toward cancer. Science. 1994 Jan 21;263(5145):319–321. doi: 10.1126/science.8278804. [DOI] [PubMed] [Google Scholar]
  13. Málková J., Michalová K., Pribyl T., Schreiber V. Chromosomal changes in rat pituitary and bone marrow induced by long-term estogen administration. Neoplasma. 1977;24(3):277–284. [PubMed] [Google Scholar]
  14. Nakamura K., Maeda H., Kawaguchi H. Enzymatic assay of hemoglobin in tissue homogenates with chlorpromazine. Anal Biochem. 1987 Aug 15;165(1):28–32. doi: 10.1016/0003-2697(87)90196-5. [DOI] [PubMed] [Google Scholar]
  15. Schechter J., Weiner R. Changes in basic fibroblast growth factor coincident with estradiol-induced hyperplasia of the anterior pituitaries of Fischer 344 and Sprague-Dawley rats. Endocrinology. 1991 Nov;129(5):2400–2408. doi: 10.1210/endo-129-5-2400. [DOI] [PubMed] [Google Scholar]
  16. Tanksley S. D. Mapping polygenes. Annu Rev Genet. 1993;27:205–233. doi: 10.1146/annurev.ge.27.120193.001225. [DOI] [PubMed] [Google Scholar]
  17. Wiklund J. A., Gorski J. Genetic differences in estrogen-induced deoxyribonucleic acid synthesis in the rat pituitary: correlations with pituitary tumor susceptibility. Endocrinology. 1982 Oct;111(4):1140–1149. doi: 10.1210/endo-111-4-1140. [DOI] [PubMed] [Google Scholar]
  18. Wiklund J., Rutledge J., Gorski J. A genetic model for the inheritance of pituitary tumor susceptibility in F344 rats. Endocrinology. 1981 Nov;109(5):1708–1714. doi: 10.1210/endo-109-5-1708. [DOI] [PubMed] [Google Scholar]
  19. Wiklund J., Wertz N., Gorski J. A comparison of estrogen effects on uterine and pituitary growth and prolactin synthesis in F344 and Holtzman rats. Endocrinology. 1981 Nov;109(5):1700–1707. doi: 10.1210/endo-109-5-1700. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES