Simple jQuery Dropdowns
Please use this identifier to cite or link to this item:
Title: The natural estrogenic compound diarylheptanoid (D3): In vitro mechanisms of action and in vivo uterine responses via estrogen receptor α
Authors: Wipawee Winuthayanon
Pawinee Piyachaturawat
Apichart Suksamrarn
Katherine A. Burns
Yukitomo Arao
Sylvia C. Hewitt
Lars C. Pedersen
Kenneth S. Korach
National Institute of Environmental Health Sciences
Mahidol University
Ramkhamhaeng University
Keywords: Environmental Science;Medicine
Issue Date: 1-Apr-2013
Citation: Environmental Health Perspectives. Vol.121, No.4 (2013), 433-439
Abstract: Background: Diarylheptanoid (D3) isolated from the medicinal plant, Curcuma comosa, has estrogenic activity.Objective: We aimed to elucidate the mechanism(s) of D3 action and compare it with that of 17β-estradiol (E2) using both in vitro and in vivo uterine models. Methods: We used human uterine (Ishikawa) cells to determine the estrogenic action of D3 on the activation and nuclear translocation of estrogen receptor α (ERα). In addition, we further charac terized the uterine response to D3 treatment in vivo. Results: D3 activated an estrogen responsive element (ERE) luciferase reporter through ERα, and molecular modeling suggested that D3 could be accommodated in the ERα binding pocket. Using modified ERα to assay ligand-dependent nuclear translocation, we observed D3-dependent ERα interaction and translocation. In mouse uteri, early-and late-phase estrogen-regulated gene responses were increased in D3-treated ovariectomized wild-type animals, in a manner similar to that of E2; no response was seen in ERα knockout animals. We observed a divergence in estrogen responses after D3 treatment: D3 induced robust DNA synthesis in uterine epithelial cells, linked to an increase in cell-cycle-related genes; however, no increase in uterine weight was observed 24 hr after treatment. D3 also affected uterine progesterone receptor expression patterns similar to E2. When D3 and E2were administered together, we observed no additive or antagonistic effects of D3 on E2. Our findings suggest that D3 is a weak estrogenic agonist compound. Conclusion: D3 is a weakly acting phytoestrogen that mimics the mitogenic responses produced by E2in an ERα-dependent manner, but it is unable to increase uterine weight or enhance or antagonize the effects of estrogen.
ISSN: 15529924
Appears in Collections:Scopus 2011-2015

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.