Discussion
In this study we characterized the estrogenic
activity of diarylheptanoids, naturally occurring compounds from C. comosa, in established in vitro and in vivo model systems.
Diarylheptanoids (D1, D2, and D3) stimulated
several endogenous estrogen-regulated genes
in MCF-7 cells in an ER-dependent manner.
Transcriptional activation of a reporter gene
required a functional AF2 region of the ER
protein. Moreover, we demonstrated that only
the D3 compound exerted ER-dependent
uterotrophic activity in WT OVX mice.
Additionally, the estrogenic activity of D3 in
the uterus was mediated through both classical and nonclassical ERE-independent mechanisms. To our knowledge, this is the first
study showing the molecular mechanism and
selectivity of these diarylheptanoids as novel
phytoestrogens
DiscussionIn this study we characterized the estrogenicactivity of diarylheptanoids, naturally occurring compounds from C. comosa, in established in vitro and in vivo model systems.Diarylheptanoids (D1, D2, and D3) stimulatedseveral endogenous estrogen-regulated genesin MCF-7 cells in an ER-dependent manner.Transcriptional activation of a reporter generequired a functional AF2 region of the ERprotein. Moreover, we demonstrated that onlythe D3 compound exerted ER-dependentuterotrophic activity in WT OVX mice.Additionally, the estrogenic activity of D3 inthe uterus was mediated through both classical and nonclassical ERE-independent mechanisms. To our knowledge, this is the firststudy showing the molecular mechanism andselectivity of these diarylheptanoids as novelphytoestrogens
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