Skip to main content
NCBI home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1995 Aug;86(8):724–729. doi: 10.1111/j.1349-7006.1995.tb02460.x

Inhibitory Effects of Medroxyprogesterone Acetate on Mouse Endometrial Carcinogenesis

Kenji Niwa 1,✉, Shigeo Morishita 1, Toshiko Murase 1, Naoki Itoh 1, Takuji Tanaka 2, Hideki Mori 2, Teruhiko Tamaya 1
PMCID: PMC5920903  PMID: 7559094

Abstract

The present study was undertaken to examine the effects of cyclic administration of low‐dose progestogen on endometrial carcinogenesis in mice. A total of 115 female ICR mice, 10 weeks of age, were divided into four experimental and control groups. Mice in groups 1–3 received laparotomy and were injected with N‐methyl‐N‐nitrosourea (MNU) solution at a dose of 1 mg/100 g body weight to the left uterine tube and with normal saline to the right uterine tube. From one week after the MNU exposure, groups 1 and 2 were given 5 ppm 17β‐estradiol (E2)‐containing diet throughout the experiment. Mice in group 1 received 5 s.c. injections of medroxyprogesterone acetate (MPA) (2 mg/ mouse) at intervals of 4 weeks from week 7. Group 3 was treated with MNU/normal saline alone. Group 4 consisted of mice treated with MPA alone. At the termination of the experiment (week 30), all animals were killed and autopsied for pathological examinations. It was found that adenocarcinomas and preneoplastic lesions developed in the bilateral uterine corpora in mice of groups 1–3. MPA treatment significantly decreased the weight of the uterine corpus (P< 0.05) and the incidences of endometrial adenocarcinoma and atypical or adenomatous (P< 0.001) but not cystic glandular hyperplasias in the MNU/E2‐treated groups. Additionally, MPA treatment tended to decrease the proliferating cell nuclear antigen‐labeling index in endometrial glandular cells. These data indicate that MPA, even at low dose, has an inhibitory effect on mouse endometrial carcinogenesis induced by MNU and E2.

Keywords: Inhibition, Carcinogenesis, Medroxyprogesterone acetate, Endometrium, Mouse

Full Text

The Full Text of this article is available as a PDF (314.1 KB).

REFERENCES

  • 1. ) Novak , E. and Yui , E.Relation of endometrial hyperplasia to adenocarcinoma of the uterus . Am. J. Obstet. Gynecol. , 32 , 674 – 679 ( 1936. ). [Google Scholar]
  • 2. ) Masubuchi , K. , Nemoto , H. , Masubuchi , S. , Fujimoto , I. and Uchino , S.Increasing incidence of endometrial carcinoma in Japan . Gynecol. Oncol. , 3 , 335 – 346 ( 1975. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Ziel , H. K.Estrogen's role in endometrial cancer . Obstet. Gynecol. , 60 , 509 – 515 ( 1982. ). [PubMed] [Google Scholar]
  • 4. ) Spicer , D. V. and Pike , M. C.The prevention of breast cancer through reduced ovarian steroid exposure . Acta Oncol. , 31 , 167 – 174 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Schlesselman , J. J.Oral contraceptives and neoplasia of the uterine corpus . Contraception , 43 , 557 – 579 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Gambrell , R. D.Prevention of endometrial cancer with progestogens . Maturitas , 8 , 159 – 168 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Gambrell , R. D.The role of hormones in the etiology and prevention of endometrial cancer . Clin. Obstet. Gynecol. , 13 , 695 – 723 ( 1986. ). [PubMed] [Google Scholar]
  • 8. ) Niwa , K. , Yokoyama , Y. , Tanaka , T. , Murase , T. , Morishita , S. , Itoh , M. , Itoh , N. , Shimokawa , K. and Tamaya , T.Successful pregnancy in a patient with endometrial carcinoma treated with medroxyprogesterone acetate . Arch. Gynecol. Obstet. , 255 , 91 – 94 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Lober , J. , Mourisden , H. T. and Rose , C.Oral or intramuscular treatment of advanced breast cancer with medroxyprogesterone acetate: a review . In “ Role of Medroxyprogesterone Acetate in Endocrine Related Tumors. Vol II ,” ed. Campio L. , della Cuna G. R. and Taylor R. W. , pp. 105 – 114 ( 1992. ). Raven Press; , New York . [Google Scholar]
  • 10. ) Taylor , R. W.The treatment of endometrial carcinoma with medroxyprogesterone acetate . In “ Role of Medroxyprogesterone Acetate in Endocrine Related Tumors. Vol. II ,” ed. Campio L. , della Cuna G. R. and Taylor R. W. , pp. 157 – 162 ( 1992. ). Raven Press; , New York . [Google Scholar]
  • 11. ) IARC Monographs on the evaluation of carcinogenic risks to humans , Vol. 21 . “ Sex Hormones, Part II ,” pp. 417 – 430 ( 1979. ). International Agency for Research on Cancer; , Lyon . [Google Scholar]
  • 12. ) Lanari , C. , Molinolo , A. A. and Pasqualini , C. D.Induction of mammary adenocarcinomas by medroxyprogesterone acetate in BALB/c female mice . Cancer Lett. , 33 , 215 – 223 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Molinolo , A. A. , Lanari , C. , Charreau , E. H. , Sanjuan , N. and Pasqualini , C. D.Mouse mammary tumors induced by medroxyprogesterone acetate: immunohistochemistry and hormonal receptors . J. Natl. Cancer Inst. , 79 , 1341 – 1350 ( 1987. ). [PubMed] [Google Scholar]
  • 14. ) Niwa , K. , Tanaka , T. , Mori , H. , Yokoyama , Y. , Furui , T. , Mori , H. and Tamaya , T.Rapid induction of endometrial carcinoma in ICR mice treated with N‐methyl‐N‐nitro‐sourea and 17β‐estradiol . Jpn. J. Cancer Res. , 82 , 1391 – 1396 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. ) Niwa , K. , Murase , T. , Furui , T. , Morishita , S. , Mori , H. , Tanaka , T. , Mori , H. and Tamaya , T.Enhancing effects of estrogens on endometrial carcinogenesis initiated by N‐methyl‐N‐nitrosourea in ICR mice . Jpn. J. Cancer Res. , 84 , 951 – 955 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. ) Poulsen , H. E. and Taylor , C. W.Histological typing of female genital tract tumors , In “ International Histological Classification of Tumours, No. 13 ,” pp. 63 – 66 ( 1975. ). WHO; , Geneva . [Google Scholar]
  • 17. ) Muñoz , N. , Dunn , T. B. and Turusov , V. S.Tumours of the vagina and uterus . In “ Pathology of Tumours in Laboratory Animals. Vol II: Tumours of the Mouse ,” ed. Turusov V. S. , IARC Scientific Publications No. 23 , pp. 359 – 383 ( 1979. ). International Agency for Research on Cancer; , Lyon . [PubMed] [Google Scholar]
  • 18. ) Hsu , S. M. , Raine , L. and Fanger , H.Use of avidin‐biotinperoxidase complex (ABC) in immunoperoxidase technique: a comparison between ABC and unlabeled antibody (PAP) procedures . J. Histochem. Cytochem. , 29 , 577 – 580 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Nagasawa , H. , Fujii , M. and Hagiwara , K.Inhibition by medroxyprogesterone acetate of precancerous mammary hyperplastic alveolar nodule formation in mice . Breast Cancer Res. Treat. , 5 , 31 – 36 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Welsch , C. W. and Nagasawa , H.Prolactin and murine mammary tumorigenesis: a review . Cancer Res. , 37 , 951 – 963 ( 1977. ). [PubMed] [Google Scholar]
  • 21. ) Whitehead , M. I. , Townsend , P. T. , Pryse‐Davies , J. , Ryder , T. , Lane , Q. , Siddle , N. C. and King , R. J.Effects of various types and dosages of progestogens on postmenopausal endometrium . J. Reprod. Med. , 27 , 539 – 548 ( 1982. ). [PubMed] [Google Scholar]
  • 22. ) Whitehead , M. I. , Townsend , P. T. , Pryse‐Davies , J. , Ryder , T. , Lane , Q. , Siddle , N. and King , R. J. B.Actions of progestins on morphology and biochemistry of the endometrium of postmenopausal women receiving lowdose estrogen therapy . Am. J. Obstet. Gynecol. , 142 , 791 – 795 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Cohen , S. M. and Ellwein , L. B.Cell proliferation in carcinogenesis . Science , 249 , 1007 – 1011 ( 1990. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES