Aromatase-independent testosterone conversion into estrogenic steroids is inhibited by a 5 alpha-reductase inhibitor.
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.
Ishikawa
Toshio
T
Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Galter Pavilion, Suite 3-150, 251 E. Huron St., Chicago, Illinois 60611-2908, USA.
Glidewell-Kenney
Christine
C
Jameson
J Larry
JL
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism / Q000494:pharmacology*; D001141:Aromatase / Q000378:metabolism* / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D013256:Steroids / Q000378:metabolism*; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004967:Estrogens; D013256:Steroids; D013739:Testosterone; D001141:Aromatase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase