Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1984 Dec;50(6):779–784. doi: 10.1038/bjc.1984.256

Preventive effects of antioestrogen on mammary and pituitary tumorigenesis in rats.

C Sumi, K Yokoro, R Matsushima
PMCID: PMC1976998  PMID: 6498074

Abstract

Six groups of inbred male Wistar/Furth (WF) rats were castrated at 40 days of age and group I received no further treatment. Groups 3 and 5 received 5.0 mg diethylstilboestrol (DES) pellets. Groups 4 and 6 were given both DES and 5.0 mg anti-oestrogen (antiE) clomiphene citrate pellets. At 50-55 days of age groups 2, 5, and 6 were exposed daily to drinking water containing 5.0 mg N-nitrosobutylurea (NBU), for 30 days. None of the castrated rats given NBU alone developed mammary or pituitary tumours (MT, PT). When antiE was administered, both MT and PT incidences were reduced in rats given DES alone or in combination with NBU. Furthermore, in antiE-treated rats receiving DES and NBU the mean number of MT per rat was also significantly decreased. Similarly a marked reduction in the mean pituitary weight was observed in antiE-treated groups. These results indicate that antiE treatment was effective in the prevention of both mammary and pituitary tumorigenesis in rats receiving DES alone or receiving a combination of DES and NBU, and its inhibitory effect on mammary tumorigenesis may be mainly due to competitive antagonism for DES-induced pituitary tumorigenesis by antiE.

Full text

PDF
779

Selected References

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

  1. Bowman S. P., Leake A., Miller M., Morris I. D. Agonist and antagonist activity of en-clomiphene upon oestrogen-mediated events in the uterus, pituitary gland and brain of the rat. J Endocrinol. 1981 Mar;88(3):367–374. doi: 10.1677/joe.0.0880367. [DOI] [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. Chen C. L., Meites J. Effects of estrogen and progesterone on serum and pituitary prolactin levels in ovariectomized rats. Endocrinology. 1970 Mar;86(3):503–505. doi: 10.1210/endo-86-3-503. [DOI] [PubMed] [Google Scholar]
  4. Gala R. R., Boss R. S. Serum prolactin levels of rats under continuous estrogen stimulation and 2 Br-alpha-ergocryptine (CB-154) injection. Proc Soc Exp Biol Med. 1975 Jun;149(2):330–332. doi: 10.3181/00379727-149-38800. [DOI] [PubMed] [Google Scholar]
  5. Gullino P. M., Pettigrew H. M., Grantham F. H. N-nitrosomethylurea as mammary gland carcinogen in rats. J Natl Cancer Inst. 1975 Feb;54(2):401–414. [PubMed] [Google Scholar]
  6. Heuson J. C., Engelsman E., Blonk-Van Der Wijst J., Maass H., Drochmans A., Michel J., Nowakowski H., Gorins A. Comparative trial of nafoxidine and ethinyloestradiol in advanced breast cancer: an E.O.R.T.C. study. Br Med J. 1975 Jun 28;2(5973):711–713. doi: 10.1136/bmj.2.5973.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jordan V. C., Koerner S. Tamoxifen as an anti-tumour agent: role of oestradiol and prolactin. J Endocrinol. 1976 Feb;68(02):305–311. doi: 10.1677/joe.0.0680305. [DOI] [PubMed] [Google Scholar]
  8. Kato J., Kobayashi T., Villec C. A. Effect of clomiphene on the uptake of estradiol by the anterior hypothalamus and hypophysis. Endocrinology. 1968 May;82(5):1049–1052. doi: 10.1210/endo-82-5-1049. [DOI] [PubMed] [Google Scholar]
  9. Katzenellenbogen B. S., Tsai T. S., Tatee T., Katzenellenbogen J. A. Estrogen and antiestrogen action: studies in reproductive target tissues and tumors. Adv Exp Med Biol. 1979;117:111–132. doi: 10.1007/978-1-4757-6589-2_6. [DOI] [PubMed] [Google Scholar]
  10. Kurl R. N., Borthwick N. M. Clomiphene and tamoxifen action in the rat uterus. J Endocrinol. 1980 Jun;85(3):519–524. doi: 10.1677/joe.0.0850519. [DOI] [PubMed] [Google Scholar]
  11. Kurl R. N., Morris I. D. Differential depletion of cytoplasmic high affinity oestrogen receptors after the in vivo administration of the antioestrogens, clomiphene, MER-25 and tamoxifen. Br J Pharmacol. 1978 Apr;62(4):487–493. doi: 10.1111/j.1476-5381.1978.tb07752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lamberts S. W., Verleun T., Oosterom R. Effect of tamoxifen administration on prolactin release by invasive prolactin-secreting pituitary adenomas. Neuroendocrinology. 1982;34(5):339–342. doi: 10.1159/000123324. [DOI] [PubMed] [Google Scholar]
  13. Lu K. H., Koch Y., Meites J. Direct inhibition by ergocornine of pituitary prolactin release. Endocrinology. 1971 Jul;89(1):229–233. doi: 10.1210/endo-89-1-229. [DOI] [PubMed] [Google Scholar]
  14. NICOLL C. S., MEITES J. Estrogen stimulation of prolactin production by rat adenohypophysis in vitro. Endocrinology. 1962 Feb;70:272–277. doi: 10.1210/endo-70-2-272. [DOI] [PubMed] [Google Scholar]
  15. Nagasawa H., Yanai R., Taniguchi H. Importance of mammary gland DNA synthesis on carcinogen-induced mammary tumorigenesis in rats. Cancer Res. 1976 Jul;36(7 Pt 1):2223–2226. [PubMed] [Google Scholar]
  16. Noteboom W. D., Durham J. B., Mitra R. Variations in the levels of estrogen receptors in prolactin producing pituitary tumor cells. J Steroid Biochem. 1982 May;16(5):633–638. doi: 10.1016/0022-4731(82)90099-1. [DOI] [PubMed] [Google Scholar]
  17. Notides A. C. The binding affinity and specificity of the estrogen receptor of the rat uterus and anterior pituitary. Endocrinology. 1970 Nov;87(5):987–992. doi: 10.1210/endo-87-5-987. [DOI] [PubMed] [Google Scholar]
  18. Odashima S. Leukemogenesis of N-nitrosobutylurea in the rat. I. Effect of various concentrations in the drinking water to female Donryu rats. Gan. 1970 Jun;61(3):245–253. [PubMed] [Google Scholar]
  19. Sumi C., Yokoro K., Kajitani T., Ito A. Synergism of diethylstilbestrol and other carcinogens in concurrent development of hepatic, mammary, and pituitary tumors in castrated male rats. J Natl Cancer Inst. 1980 Jul;65(1):169–175. [PubMed] [Google Scholar]
  20. Sumi C., Yokoro K., Matsushima R. Suppression of diethylstilbestrol and N-nitrosobutylurea-induced mammary and pituitary tumorigenesis in rats by prolonged treatment with 2-bromoergocryptine. Cancer Res. 1983 Oct;43(10):4781–4785. [PubMed] [Google Scholar]
  21. de Quijada M., Timmermans H. A., Lamberts S. W. Tamoxifen suppresses both the growth of prolactin-secreting pituitary tumours and normal prolactin synthesis in the rat. J Endocrinol. 1980 Jul;86(1):109–116. doi: 10.1677/joe.0.0860109. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES