Skip to main content
SpringerLink
Log in

Adrenal steroids stimulate growth and progesterone receptor levels in rat uterus and DMBA-induced mammary tumors

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

We have studied the effect of treatment with the adrenal steroids androst-5-ene-3β,17β-diol (Δ5-diol) and dehydroepiandrosterone (DHEA) on the growth and progesterone receptor levels of dimethylbenz-(a)anthracene (DMBA)-induced mammary tumors in the rat.

While the total number of tumors in ovariectomized animals was 0.60 ± 0.19 tumor per rat after 24 days, it increased to 2.54 ± 0.50 (p<0.01) and 1.42 ± 0.26 (p<0.01) in the Δ5-diol and DHEA (2 mg, twice daily) treated animals, respectively. While very few new tumors developed during a 24-day period in ovariectomized animals (0.07 ± 0.07/rat), an average of 0.47 ± 0.19 (p<0.05) new tumor per animal appeared in intact rats. In ovariectomized animals treated with Δ5-diol or DHEA, the numbers of new tumors were 0.77 ± 0.26 (p<0.05) and 0.42 ± 0.15 (p<0.05), respectively. An even more striking effect was observed on average total tumor area, which decreased from 4.70 ± 0.95 cm2 in intact animals to 0.75 ± 0.27 cm2 (p<0.01) following ovariectomy. Values of 9.79 ± 2.25 (p<0.01) and 3.93 ± 0.86 cm2 (p<0.01) were found in the Δ5-diol- and DHEA-treated ovariectomized animals, respectively.

Treatment of ovariectomized animals with Δ5-diol and DHEA caused a marked increase (p<0.01) in progesterone receptor levels in both the uteri and DMBA-induced mammary tumors. Uterine weight was also stimulated (p<0.01) by treatment with the two adrenal steroids.

The present data show that two adrenal C19-Δ5 steroids, Δ5-diol and DHEA, possess stimulatory effects analogous to those of estrogens on DMBA-induced mammary tumor growth and progesterone receptor levels in the rat, thus supporting the suggestion of an important role of these adrenal steroids in breast cancer and other estrogen-sensitive diseases in the human.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Huggins C, Grand LC, Brillantes FP: Mammary cancer induced by a single feeding of polynuclear hydrocarbons, and its suppression. Nature 189: 204–207, 1961

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  3. Asselin J, Labrie F: Effects of estradiol and prolactin on steroid receptor levels in 7,12-dimethylbenz(a)anthracene-induced mammary tumors and uterus in the rat. J Steroid Biochem 9: 1079–1082, 1977

    Google Scholar 

  4. Jones D, Cameron EHD, Griffiths K, Gleave EN, Forrest APM: Steroid metabolism by human breast tumours. Biochem J 116: 919–925, 1970

    PubMed  Google Scholar 

  5. Miller WR, McDonald D, Forrest APM, Shivas AA: Metabolism of androgens by human breast tissue. Lancet i: 912, 1973

    Google Scholar 

  6. Griffiths K, Jones D, Cameron EHD, Gleave EN, Forrest APM: Transformation of steroids by mammary carcinoma tissue. In: Dao TL (ed): Estrogen Target Tissues and Neoplasia. University of Chicago Press, Chicago, 1972, pp 151–162

    Google Scholar 

  7. Adams JB, Li K: Biosynthesis of 17β-estradiol in human breast carcinoma tissue and a novel method for its characterization. Br J Cancer 31: 429–433, 1975

    PubMed  Google Scholar 

  8. Van Doorn LG, Poortman J, Thijssen JHH, Schwartz F: Actions and interactions of 5-androstene-3β,17β-diol and estradiol-17β in the immature rat uterus. Endocrinology 108: 1587–1593, 1981

    PubMed  Google Scholar 

  9. Seymour-Munn K, Adams J: Estrogenic effects of 5-androstene-3β,17β-diol at physiological concentrations and its possible implication in the etiology of breast cancer. Endocrinology 112: 486–491, 1983

    PubMed  Google Scholar 

  10. Adams JB, Garcia M, Rochefort H: Estrogenic effects of physiological concentrations of 5-androstene-3β,17β-diol and its metabolism in MCF-7 human breast cancer cells. Cancer Res 41: 4720–4726, 1981

    PubMed  Google Scholar 

  11. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275, 1951

    PubMed  Google Scholar 

  12. Asselin J, Labrie F, Kelly PA, Philibert D, Raynaud JP: Specific progesterone receptors in dimethylbenz(a)-anthracene (DMBA)-induced mammary tumors. Steroids 27: 395–404, 1976

    PubMed  Google Scholar 

  13. Asselin J, Mélançon R, Gourdeau Y, Labrie F, Bonne C, Raynaud JP: Specific binding of [3H]methyltrienolone to both progestin and androgen binding components in human benign prostatic hypertrophy (BPH). J Steroid Biochem 10: 483–486, 1979

    PubMed  Google Scholar 

  14. Kramer CY: Extension of multiple range tests to group means with unequal numbers of replications. Biometrics 12: 307–310, 1956

    Google Scholar 

  15. Adams J: Control of secretion and the function of C19 Δ5-steroids of the human adrenal gland. Mol Cell Endocrinol 41: 1–17, 1985

    PubMed  Google Scholar 

  16. Huggins C, Briziarelli G, Sutton Jr H: Rapid induction of mammary carcinoma in the rat and the influence of hormones on the tumors. J Expl Med 109: 25–41, 1959

    Google Scholar 

  17. Talwalker PK, Meites J, Mizuno H: Mammary tumor induction by estrogen or anterior pituitary hormones in ovariectomized rats given 7,12-dimethylbenz(a)anthracene. Proc Soc Exp Biol Med 116: 531–534, 1964

    PubMed  Google Scholar 

  18. Leung BS, Sasaki GH, Leung JS: Estrogen-prolactin dependency in 7,12-dimethylbenz(a)anthracene-induced tumors. Cancer Res 35: 621–627, 1975

    PubMed  Google Scholar 

  19. Poortman J, Vroegindewey-Jie D, Thijssen JHH, Schwarz F: Relative binding affinity of androstane and C-19-nor-androstane steroids for the estradiol receptor in human myometrial and mammary cancer tissue. Mol Cell Endocrinol 8: 27–34, 1977

    PubMed  Google Scholar 

  20. Poulin R, Labrie F: Estrogenic effect of adrenal steroids in the human mammary carcinoma cell line ZR 75-1. In: Genazzani AR (ed): Frontiers in Gynecological Endocrinology. Parthenon, London, in press

  21. Maroulis GB, Abraham GE: Ovarian and adrenal contribution to peripheral steroid levels in post-menopausal women. Obstet Gynecol 48: 150–154, 1976

    PubMed  Google Scholar 

  22. Rosenfield RL, Otto P: Androstenediol levels in human peripheral plasma. J Clin Endocrinol Metab 35: 818–822, 1972

    PubMed  Google Scholar 

  23. Bird CE, Morrow L, Fukumoto Y, Marcellus S, Clark AF: Δ5-androstenediol: kinetics of metabolism and binding to plasma proteins in normal men and women. J Clin Endocrinol Metab 43: 1317–1322, 1976

    PubMed  Google Scholar 

  24. Bird CE, Murphy J, Boroomand K, Finnis W, Dressel D, Clark AF: Dehydroepiandrosterone: kinetics of metabolism in normal men and women. J Clin Endocrinol Metab 47: 818–822, 1978

    PubMed  Google Scholar 

  25. Adams JB, Archibald L, Seymour-Munn K: Dehydro-epiandrosterone and androst-5-ene-3β,17β-diol in human mammary cancer cytosolic and nuclear compartments and their relationship to estrogen receptor. Cancer Res 40: 3815–3820, 1980

    PubMed  Google Scholar 

  26. Bonney RC, Scanlon MJ, Reed MJ, Jones DL, Beranek PA, James VHT: Adrenal androgen concentrations in breast tumours and in normal breast tissue. The relationship to oestradiol metabolism. J Steroid Biochem 20: 501–504, 1984

    PubMed  Google Scholar 

  27. van Landeghem AAJ, Poortman J, Nabuurs M, Thijssen JHH: Endogenous concentration and subcellular distribution of androgens in normal and malignant human breast tissue. Cancer Res 45: 2907–2912, 1985

    PubMed  Google Scholar 

  28. Adams JB, Wong MSF: Paraendocrine behaviour of human breast carcinoma.In vitro transformation of steroids to physiologically active hormones. J Endocrinol 41: 41–52, 1968

    Google Scholar 

  29. Li K, Foo T, Adams JB: Products of dehydroepiandrosterone metabolism by human mammary tumors and their influence on estradiol receptor binding. Steroids 31: 113–127, 1978

    PubMed  Google Scholar 

  30. Siiteri PK, McDonald DC: The role of extraglandular estrogens in human endocrinology. In: Geiger SR, Astwood EB, Greep RO (eds): Handbook of Physiology, Section 7. The American Physiology Society, New York, 1973, pp 615–619

    Google Scholar 

  31. Carlström K: Influence of intratumoral estradiol biosynthesis on estrogen receptors. In: Leclercq G, Toma S, Paridaens R, Heuson JC (eds): Recent Results in Cancer Research, Vol. 91. Springer-Verlag, Berlin, 1984, pp 145–149

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MRC Group in Molecular Endocrinology, Laval University Medical Center, 2705 Laurier Boulevard, G1V 4G2, Quebec, Canada

    Paulo G. Spinola, Bianca Marchetti & Fernand Labrie

Authors
  1. Paulo G. Spinola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bianca Marchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fernand Labrie
    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

Spinola, P.G., Marchetti, B. & Labrie, F. Adrenal steroids stimulate growth and progesterone receptor levels in rat uterus and DMBA-induced mammary tumors. Breast Cancer Res Tr 8, 241–248 (1986). https://doi.org/10.1007/BF01807337

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01807337

Keywords

Search

Navigation