Aromatase-independent testosterone conversion into estrogenic steroids is inhibited by a 5 alpha-reductase inhibitor

J Steroid Biochem Mol Biol. 2006 Feb;98(2-3):133-8. doi: 10.1016/j.jsbmb.2005.09.004. Epub 2005 Dec 28.


Estrogens are generated mainly by the action of aromatase, which converts testosterone to estradiol and androstenedione to estrone. However, in addition to estradiol and estrone, a variety of other steroids, whose synthesis is not dependent on aromatase, can stimulate the estrogen receptor. Here we show that testosterone is converted into such estrogenic steroids by aromatase-negative HeLa cells. This aromatase-independent generation of estrogenic steroids is seen in aromatase-positive MCF-7 cells as well. In both cell lines, the synthesis of estrogenic steroids was blocked by inhibition of testosterone conversion into dihydrotestosterone using a 5 alpha-reductase inhibitor finasteride, suggesting that they are generated downstream of dihydrotestosterone. This finding raises the possibility that the combination of a 5 alpha-reductase inhibitor and an aromatase inhibitor may reduce estrogenic steroids in vivo more completely than an aromatase inhibitor alone.

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / pharmacology*
  • Aromatase / metabolism*
  • Aromatase / pharmacology
  • Estrogens / metabolism*
  • Female
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Models, Biological
  • Steroids / metabolism*
  • Testosterone / antagonists & inhibitors
  • Testosterone / metabolism*
  • Tumor Cells, Cultured


  • Estrogens
  • Steroids
  • Testosterone
  • Aromatase
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase