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The Roles of Estrogen and Progestin in Producing Deciduosarcoma and Other Lesions in the Rabbit

Center for Biomedical Research, Population Council, New York, New York 10021

Bernard C. Zook

The Department of Pathology, The George Washington University Medical Center, Washington, DC 20037

Ashok K. Didolkar

Center for Biomedical Research, Population Council, New York, New York 10021

Kalyan Sundaram

Center for Biomedical Research, Population Council, New York, New York 10021

Harold A. Nash

Center for Biomedical Research, Population Council, New York, New York 10021

The interactions of estrogens and progestins in producing decidualization, deciduosarcoma, and other lesions in the rabbit were explored. Steroids were delivered by silicone elastomer implants placed subdermally except for oral dosing in 1 experiment. Varying doses of levonorgestre l (LNG) were given with and without estradiol (E ₂) and varying doses of E₂ with and without LNG. LNG alone delivered at an estimated mean dose of 233 µg/day did not result in endometrial decidualization or deciduosarcoma. Both conditions occurred when E₂ was added to the regimen and increased as the dose of E₂ was increased. Sixty µg of E₂ per day produced endometrial decidualization in all test animals in a 2-month exposure, but deciduosarcom a occurred only when LNG was also supplied and increased as the LNG dose was increased. Progesterone given with E₂ resulted in deciduosarcoma in most rabbits. Ethynylestradiol alone at 30 µ g/day delivered by implants produced splenic and ovarian deciduosarcoma s in 1 of 5 test animals. Adding LNG resulted in more numerous and widespread deciduosarcomas. These experiments indicate that exogenous estrogen is necessary for decidualization of the endometrium and to production of deciduosarcoma in the nonpregnant rabbit. Exogenous progestin promotes the process. Necrosis of the uterine wall tended to increase with increasing dose of estrogens.

Key Words: Decidual tumors • endometrium • estrogen • progestins • rabbits • uteroglobin • uterus.

Toxicologic Pathology, Vol. 29, No. 4, 417-421 (2001)
DOI: 10.1080/01926230152499764


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				B. C. Zook, O. A. Janne, A. A. Abraham, and H. A. Nash The Development and Regression of Deciduosarcomas and Other Lesions Caused by Estrogens and Progestins in Rabbits Toxicol Pathol, June 1, 2001; 29(4): 411 - 416. [Abstract] [PDF]