Abstract
Background: Progesterone is metabolized in the normal breast mainly into 4-ene-pregnenes (e.g. 20α-dihydroprogesterone, 20αDHP) but, in contrast, in breast cancer tissue the 5α-dihydropregnanes (e.g. 5α-dihydroprogesterone, 5αDHP) are prevalent. In the present study the effect of progesterone and its main metabolites 20αDHP and 5αDHP on the aromatase activity in a stable aromatase-expressing estrogen receptor-positive human breast cancer cell line, MCF-7aro, was explored. Materials and Methods: The MCF-7aro cells were stripped of endogenous steroids and incubated with physiological concentrations of [3H]-testosterone ([3H]-testos: 5×10-9M) alone or in the presence of progesterone, 20αDHP or 5αDHP (5×10-6 or 5×10-8M) for 24 h at 37°C. The cellular radioactivity uptake was determined in the ethanolic supernatant and the DNA content in the remaining pellet. [3H]-Estradiol (E2), [3H]-estrone (E1) and [3H]-testos were characterized by thin layer chromatography and quantified using the corresponding standard. Results: Aromatase activity was present at a high level in the MCF-7aro cells after incubation with [3H]-testos when the concentration of [3H]-E2 was 3.70 pmol/mg DNA; 20αDHP at concentrations of 5×10-6M or 5×10-8M significantly inhibited this conversion by 50.3% and 36.5%, respectively. No significant effect was found with the metabolite 5αDHP or the parent hormone, progesterone. Conclusion: The MCF-7aro cell line shows high detectable aromatase activity. The present data indicate that the progesterone metabolite 20αDHP, found mainly in normal breast tissue, can act as an anti-aromatase agent.
Footnotes
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↵* Present address: AP-HP, CHU Bicêtre, and INSERM U693, Faculté de Médecine Paris-Sud, 94276 Le Kremlin-Bicêtre, France. e-mail: gerard.chetrite{at}u-psud.fr
- Received March 4, 2008.
- Revision received May 22, 2008.
- Accepted May 26, 2008.
- Copyright© 2008 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved