Skip to main content

Antiestrogen action of progesterone in breast tissue

Breast Cancer Research and Treatment volume 8, pages 179–188 (1986)Cite this article

Abstract

In normal breast, estrogen stimulates growth of the ductal system, while lobular development depends on progesterone. Thus, estrogen and progesterone, when secreted in an adequate balance, permit the complete and proper development of the mammary gland. Progesterone may also have an antagonistic activity against estradiol, mediated through a decrease in the replenishment of the estrogen receptor, and also through increased 17β-hydroxysteroid dehydrogenase which leads to accelerated metabolism of estradiol to estrone in the target organ. Thus, it can be inferred that long periods of luteal phase defect leading to an unopposed estrogen effect on the breast might promote breast carcinogenesis.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. Asboe-Hansen G: Hormonal effects on connective tissue. Physiol Rev 38: 446–462, 1958

    PubMed  Google Scholar 

  2. Asselin J, Kelly PA, Caron MG, Labrie F: Control of hormone receptor levels and growth of 7,12-dimethyl benz(a)anthracene induced mammary tumors by estrogens, progesterones and prolactin. Endocrinology 101: 666–671, 1977

    PubMed  Google Scholar 

  3. Bardon S, Vignon F, Chalbos D, Rochefort H: RU 486, a progestin and glucocorticoid antagonist, inhibits the growth of breast cancer cells via the progesterone receptor. J Clin Endocrinol Metab 60: 692–697, 1985

    PubMed  Google Scholar 

  4. Bassler R: The morphology of hormone induced structural changes in female breast. Curr Top Pathol 53: 1–89, 1970

    PubMed  Google Scholar 

  5. Bayard F, Damilano S, Robel P, Baulieu EE: Cytoplasmic and nuclear estradiol and progesterone receptors in human endometrium. J Clin Endocrinol Metab 46: 635–648, 1948

    Google Scholar 

  6. Clark JM, Hsueh AJW, Peck EJ: Regulation of estrogen receptor replenishment by progesterone. Ann N Y Acad Sci 286: 161–169, 1977

    PubMed  Google Scholar 

  7. Clark JH, Markaverich BM: The effects of progesterone and dexamethasone on estradiol binding and uterine growth. In: Bardin CW, Milgrom E, Mauvais-Jarvis P (eds): Progesterone and Progestins. Raven Press, New York, 1983, pp 163–177

    Google Scholar 

  8. Cowie AT, Folley SJ, Malpress FH, Richardson KC: Studies on the hormonal induction of mammary growth and lactation in the goat. J Endocrinol 8: 64–88, 1952

    PubMed  Google Scholar 

  9. Cuzick J, Wang DY, Bulbrook RD: The prevention of breast cancer. Lancet i: 83–86, 1986

    Google Scholar 

  10. Eisen MJ: The occurence of benign and malignant mammary lesions in rats treated with crystalline estrogen. Cancer Res 2: 632–644, 1942

    Google Scholar 

  11. Fournier S, Kuttenn F, De Cicco F, Baudot N, Mallet C, Mauvais-Jarvis P: Estradiol 17β-hydroxysteroid dehydrogenase activity in human breast fibro-adenomas. J Clin Endocrinol Metab 55: 428–433, 1982

    PubMed  Google Scholar 

  12. Gompel A, Malet C, Spitzer P, Lalardrie JP, Kuttenn F, Mauvais-Jarvis P: Progestin effect on cell multiplication and 17β-hydroxy steroid dehydrogenase activity in normal human breast cells in culture. J Clin Endocrinol Metab 63: 1174–1179, 1986

    PubMed  Google Scholar 

  13. Gottardis M, Erturk E, Rose DP: Effects of progesterone administration on N-nitrosomethyl urea-induced rat mammary carcinogenesis. Eur J Cancer Clin Oncol 19: 1479–1484, 1983

    PubMed  Google Scholar 

  14. Grubbs CJ, Farnell DR, Hill DL, McDonough KC: Chemoprevention of N-nitroso-N-methylurea induced mammary cancers by pretreatment with 17β-estradiol and progesterone. J Natl Cancer Inst 74: 927–931, 1985

    PubMed  Google Scholar 

  15. Gurpide E: Antiestrogenic actions of progesterone and progestins in women. In: Bardin CW, Milgrom E, Mauvais-Jarvis P (eds): Progesterone and Progestins. Raven Press, New York, 1983, p. 149–161

    Google Scholar 

  16. Horwitz KB, Koseki Y, McGuire WL: Estrogen control of progesterone receptor in human breast cancer: role of estradiol and antiestrogen. Endocrinology 103: 1742–1747, 1978

    PubMed  Google Scholar 

  17. Horwitz KB, McGuire WL: Estrogen control of progesterone receptor in human breast cancer. Correlation with nuclear processing of estrogen receptor. J Biol Chem 253: 2223–2228, 1978

    PubMed  Google Scholar 

  18. Horwitz KB, Freidenberg GR: Growth inhibition and increase of insulin receptors in antiestrogen resistant T47Dco human breast cancer cells by progestins: implication for endocrine therapies. Cancer Res 45: 167–173, 1985

    PubMed  Google Scholar 

  19. Horwitz KB: The antiprogestin RU 38486: Receptor mediated and antiprogestin action screened in estrogen insensitive T47Dco human breast cancer cells. Endocrinology 116: 2236–2245, 1985

    PubMed  Google Scholar 

  20. Horwitz KB, Wei LL, Sedlacek SM, D'Arville CN: Progestin action and progesterone receptor structure in human breast cancer: a review. Rec Progr Horm Res 41: 249–316, 1985

    PubMed  Google Scholar 

  21. Inoh A, Kamiya K, Fujii Y, Yokoro K: Protective effects of progesterone and tamoxifen in estrogen induced mammary carcinogenesis in ovariectomized W/Fu rats. Jpn Cancer Res (Gann) 76: 699–704, 1985

    Google Scholar 

  22. Kledzik GS, Bradley CJ, Meites J: Reduction of carcinogen induced mammary cancer. Incidence in rats by early treatment with hormones or drugs. Cancer Res 34: 2953–2956, 1974

    PubMed  Google Scholar 

  23. Korenman SG: The endocrinology of breast cancer. Cancer 46: 874–878, 1980

    PubMed  Google Scholar 

  24. Kreitman O, Kreitman-Gimbal B, Bayard F, Hodgen GD: 17β-hydroxysteroid dehydrogenase in monkey endometrium: characterization of enzyme activity and effects of estradiol alone or in combination with progesterone. Steroids 34: 693–697, 1979

    PubMed  Google Scholar 

  25. Kreitman O, Bayard F, Hodgen GD: 17β-hydroxysteroid dehydrogenase in monkey endometrium during the menstrual cycle and at the time of implantation. Steroids 36: 2674–2682, 1980

    Google Scholar 

  26. Kuttenn F, Fournier S, Durand JC, Mauvais-Jarvis P: Estradiol and progesterone receptors in human breast fibroadenomas. J Clin Endocrinol Metab 52: 1225–1229, 1981

    PubMed  Google Scholar 

  27. Leavitt WW, Chen TJ, Do YS, Carlton BD, Allen TC: Biology of progesterone receptors. In: O'Malley BW, Birnbaumer L (eds): Receptors and Hormone Action, II. Acad Press, New York p 157–188, 1978

    Google Scholar 

  28. Lyons WR, McGinty DA: Effects of estrone and progesterone on male rabbit mammary glands. I. Varying doses of progesterone. Proc Soc Exp Biol Med 48: 83–89, 1941

    Google Scholar 

  29. Mauvais-Jarvis P, Sitruk-Ware R, Kuttenn F, Sterkers N: Luteal phase insufficiency: a common pathophysiologic factor in development of benign and malignant breast diseases. In: Bulbrook RD, Taylor DJ (eds): Commentaries on Research in Breast Disease. Alan Liss, New York, 1979, p 25–59

    Google Scholar 

  30. Mauvais-Jarvis P, Sitruk-Ware R, Kuttenn F: Benign breast disease. In: McGuire WL (ed): Breast Cancer, Advances in Research and Treatment. Plenum Press, New York, 1981, p 51–94

    Google Scholar 

  31. Mauvais-Jarvis P, Sitruk-Ware R, Kuttenn F: Luteal phase defect and breast cancer genesis. Breast Cancer Res Treat 2: 139–150, 1982

    PubMed  Google Scholar 

  32. Mauvais-Jarvis P: Current hormonal therapy of benign breast disease. In: Krieger DT, Bardin CW (eds): Current Therapy in Endocrinology. BC Decker, Philadelphia, 1983, p 428–432

    Google Scholar 

  33. Mauvais-Jarvis P, Kuttenn F, Gompel A: Estradiolprogesterone interaction in normal and pathological cells. Ann N Y Acad Sci 464: 152–167, 1986

    PubMed  Google Scholar 

  34. McManus MJ, Welsch CW: The effects of estrogen, progesterone, and human placental lactogen on DNA synthesis on human breast ductal epithelium maintained in athymic mice. Cancer 54: 1920, 1984

    PubMed  Google Scholar 

  35. Mowszowicz I, Bieber DE, Chung KW, Bullock LP, Bardin WL: Synandrogenic and antiandrogenic effects of progestins: comparison with non-progestational antiandrogens. Endocrinology 95: 1589–1594, 1974

    PubMed  Google Scholar 

  36. Philibert D, Deraedt R, Teutsch G, Tournemine C, Sakiz E: RU 486: A new lead for steroidal antihormones. 64th Annual Meeting of the Endocrine Society, San Francisco CA Abstr. 668, 1982

  37. Pike MC, Henderson BE, Krailo MD, Duke A, Roy S: Breast cancer in young women and use of oral contraception: Possible modifying effect of formulation and age at use. Lancet ii: 926–929, 1983

    Google Scholar 

  38. Pike MC: Breast cancer and oral contraceptives. Lancet ii: 1180–1181, 1985

    Google Scholar 

  39. Pollow K, Lubbert N, Boquoi E, Kreuzer G, Jeske R, Pollow B: Studies on 17β-hydroxysteroid dehydrogenase in human endometrium and endometrial carcinoma. Acta Endocrinol 79: 134–141, 1975

    PubMed  Google Scholar 

  40. Prudhomme JF, Malet C, Gompel A, Lalardrie JP, Boue A, Mauvais-Jarvis P, Kuttenn F: 17β-hydroxysteroid dehydrogenase (E2 DH) activity in human breast epithelial cell and fibroblast in cultures. Endocrinology 114: 1483–1489, 1984

    PubMed  Google Scholar 

  41. Segaloff A: Inhibition by progesterone of radiationestrogen induced mammary cancer in the rat. Cancer Res 33: 1136–1138, 1973

    PubMed  Google Scholar 

  42. Sitruk-Ware R, Sterkers N, Mowszowicz I, Mauvais-Jarvis P: Inadequate corpus luteal function in women with benign breast diseases. J Clin Endocrinol Metab 44: 771–774, 1977

    PubMed  Google Scholar 

  43. Tseng L, Gurpide E: Estradiol and 20α-dihydroprogesterone dehydrogenase activities in human endometrium during the menstrual cycle. Endocrinology 94: 419–423, 1974

    PubMed  Google Scholar 

  44. Tseng L, Gurpide E: Induction of human endometrial estradiol dehydrogenase by progestins. Endocrinology 97: 825–833, 1975

    PubMed  Google Scholar 

  45. Tseng L, Gusberg SB, Gurpide E: Estradiol receptor and 17β-dehydrogenase in normal and abnormal endometrium. Ann N Y Acad Sci 286: 190–198, 1977

    PubMed  Google Scholar 

  46. Vignon F, Bardon S, Chalbos D, Rochefort H: Antiestrogenic effect of R5020, a synthetic progestin, in human breast cancer cells in culture. J Clin Endocrinol Metab 56: 1124–1130, 1983

    PubMed  Google Scholar 

  47. Welsch CH, Clemens JA, Meites J: Effects of multiple pituitary homografts or progesterone on 7,12-dimethyl-benzanthracene induced mammary tumors in rats. J Natl Cancer Inst 41: 465–478, 1968

    PubMed  Google Scholar 

  48. Zarbl H, Sukumar S, Arthur AV, Martin-Zanca D, Barbacid M: Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats. Nature 315: 382–385, 1985

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Reproductive Endocrinology Necker Faculty of Medicine, 149 rue de Sèvres, 75743, Paris Cedex 15, France

    P. Mauvais-Jarvis, F. Kuttenn & A. Gompel

Authors
  1. P. Mauvais-Jarvis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Kuttenn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Gompel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mauvais-Jarvis, P., Kuttenn, F. & Gompel, A. Antiestrogen action of progesterone in breast tissue. Breast Cancer Res Tr 8, 179–188 (1986). https://doi.org/10.1007/BF01807330

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01807330

Keywords

  • antiestrogen
  • antiprogestin
  • estrogen action
  • luteal phase defect
  • mammary differentiation
  • progesterone
  • tumor promotion