Characterization of the estrogenic activity of a synthetic adrenal steroid 17-α ethinyl androstenediol and its potential use in hormone replacement therapy.

• Main Author: Tan, Vanessa Yuzhen.
• Other Authors: Vaninirappuputhenpurayil Gopalan Reju
• Format: Theses and Dissertations
• Language: English
• Published: 2011
• Subjects: DRNTU::Science::Biological sciences::Human anatomy and physiology::Endocrinology
• Online Access: http://hdl.handle.net/10356/45321
• Institution: Nanyang Technological University

This study demonstrates the estrogenic activity of 17-alpha ethinyl androstenediol (AED) in ER positive breast cancer cells MCF 7, T47D and CRL 1500 cells. Our findings suggest that AED binds to ER as AED significantly stimulated growth of ER positive breast cancer cells and induced the expression of progesterone receptor in MCF 7 cells whose expression is ER-dependent. In addition, gene expression studies have shown that AED significantly induces the expression of ER-target genes in ER positive breast cancer cells. This study is also the first to reveal that AED may have tissue-specific effects as it does not stimulate the growth of endometrial carcinoma cells and mouse uterine tissues. The lack of estrogenic activity of AED in the uterus is further confirmed by gene expression studies. Moreover, findings in this study also reveal that AED has promoter-specific activity in uterine tissues. The tissue-specific activity of AED raises the possibility of its use in hormonal replacement therapy. As treatment with AED does not result in endometrial hyperplasia, the additional use of a progestin to protect against endometrial proliferation is not needed, thus avoiding the increased risk of breast cancer associated with progestin usage. However, in light of the potential of AED to enhance the growth of breast carcinoma cells, a thorough check of the family history and genetic predisposition of a given individual should be carried out to weigh out the potential risks and benefits of taking AED before recommending the treatment.