Breast Cancer Research and Treatment

, Volume 12, Issue 3, pp 287–296

Effects of the aromatase inhibitor 4-hydroxyandrostenedione and the antiandrogen flutamide on growth and steroid levels in DMBA-induced rat mammary tumors

Authors

  • Paulo G. Spinola
    • MRC Group in Molecular EndocrinologyLaval University Medical Center
  • Bianca Marchetti
    • MRC Group in Molecular EndocrinologyLaval University Medical Center
  • Yves Mérand
    • MRC Group in Molecular EndocrinologyLaval University Medical Center
  • Alain Bélanger
    • MRC Group in Molecular EndocrinologyLaval University Medical Center
  • Fernand Labrie
    • MRC Group in Molecular EndocrinologyLaval University Medical Center
Report

DOI: 10.1007/BF01811241

Cite this article as:
Spinola, P.G., Marchetti, B., Mérand, Y. et al. Breast Cancer Res Tr (1988) 12: 287. doi:10.1007/BF01811241

Summary

Using dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in the rat as model, comparison was made of the effect of treatment for 20 days with the aromatase inhibitor 4-hydroxyandrostenedione (4-OH-A) (7.5 mg, twice daily) or the antiandragen flutamide (5 mg, twice daily) on tumor growth as well as on plasma and tumor content of estrogens, androgens, and their precursors and metabolites. Tumor number and size were markedly decreased following treatment with either drug, the effect of treatment being more important on size than number, and on new tumors which developed during treatment than on tumors already present at start of treatment. Treatment with the aromatase inhibitor 4-OH-A caused a parallel decrease in plasma and tumor levels of pregnenolone (Preg), progesterone (P), and 17-OH P, while there was a marked increase in dehydroepiandrosterone (DHEA), androst-5-ene-3β,17β-diol (Δ5-diol), androstenedione (Δ4-dione), testosterone (T), androstane-3α, 17β-diol (3α-diol), and androstane-3β, 17β-diol (3β-diol), with no significant change in dihydrotestosterone (DHT) and 17β-estradiol levels. The marked increase in tissue T content coupled to a decrease in P levels could well contribute to the inhibition of tumor growth induced by 4-OH-A. Flutamide, on the other hand, caused a marked fall in plasma and tissue levels of Preg, 17-OH Preg, P, and 17-OH P, with no significant change in the concentration of the other steroids, thus suggesting a possible role of the fall in tissue P levels in the inhibition of tumor growth. Since both drugs are potent inhibitors of DMBA-induced tumor growth in intact animals, better knowledge of their mechanism of action should add to our understanding of the multiple endocrine factors controlling the growth of these tumors.

Key words

aromatase inhibitor4-hydroxyandrostenedioneantiandrogenflutamidesteroid metabolismDMBA-induced rat mammary tumorsbreast cancer

Copyright information

© Kluwer Academic Publishers 1988