Abstract
Objective
Androstenedione (A4) is an androgen that can be metabolized by aromatase to estrone, but the effects
of A4 on endometrial cell proliferation either as an androgen or via conversion to estrogens
are unknown. The aim of this study was to investigate A4 effects on Ishikawa cells in culture.
Study design
Ishikawa cells were treated with increasing concentrations of A4 (0–1000 pmol) for 4 days. Cell proliferation was measured by the (4,5-dimethylthiaxol-2-yi)-2,5-diphenyltetraxolium
bromide (MTT) assay. Apoptosis was analyzed through Annexin-V/propidium iodide (PI)
staining and flow cytometry: 17β-hydroxy steroid dehydrogenase type 1 (17β-HSD1) and
aromatase mRNA expression was measured by reverse transcription-polymerase chain reaction
(RT-PCR). Western blotting was used to detect cell signaling expressions of Akt/MAPK.
Results
A4 treatment (1 nM) decreased cell proliferation and increased apoptosis, as demonstrated by MTT and
flow cytometry or related gene expression. The cellular responses induced by A4 treatment were mediated by activation of the Akt and MAPK signaling pathway. Treatment
had no effect on 17β-HSD1 and aromatase expression.
Conclusion
A4 treatment induced growth inhibition and apoptosis of Ishikawa cells through activation
of the Akt/MAPK pathway. Effects of A4 on Ishikawa cells occurred in the absence of increased 17β-HSD1 and aromatase expression.
These results imply that women with excessive androgen, such as polycystic ovary syndrome,
experience poor reproductive outcomes through androgen-regulated mechanisms.
Keywords
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Article info
Publication history
Published online: October 17, 2013
Accepted:
September 18,
2013
Received in revised form:
June 29,
2013
Received:
April 6,
2013
Identification
Copyright
© 2013 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
