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Biological characterization of non-steroidal progestins from botanicals used for women’s health.

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Title: Biological characterization of non-steroidal progestins from botanicals used for women’s health.
Author(s): Toh, MF; Sohn, J; Chen, SN; Yao, P; Bolton, JL; Burdette, JE
Abstract: Progesterone plays a central role in women’s reproductive health. Synthetic progestins, such as medroxyprogesterone acetate (MPA) are often used in hormone replacement therapy (HRT), oral contraceptives, and for the treatment of endometriosis and infertility. Although MPA is clinically effective, it also promiscuously binds to androgen and glucocorticoid receptors (AR/GR) leading to many undesirableside effects including cardiovascular diseases and breast cancers. Therefore, identifying alternative progestins is clinically significant. The purpose of this study was to biologically characterize non-steroidal progestins from botanicals by investigating their interaction and activation of progesterone receptor (PR). Eight botanicals commonly used to alleviate menopausal symptoms were investigated to determine if they contain progestins using a progesterone responsive element (PRE) luciferase reporter assay and a PR polarization competitive binding assay. Red clover extract stimulated PRE-luciferase and bound to PR. A library of purified compounds previously isolated from red clover was screened using the luciferase reporter assay. Kaempferol identified in red clover and a structurally similar flavonoid, apigenin, bound to PR and induced progestegenic activity and P4 regulated genes in breast epithelial cells and human endometrial stromal cells (HESC). Kaempferol and apigenin demonstrated higher progestegenic potency in the HESC compared to breast epithelial cells. Furthermore, phytoprogestins were able to activate P4 signaling in breast epithelial cells without downregulating PR expression. These data suggest that botanical extracts used for women’s health may contain compounds capable of activating progesterone receptor signaling.
Issue Date: 2012-06
Publisher: Elsevier
Citation Info: Toh MF, Sohn J, Chen SN, Yao P, Bolton JL, Burdette JE. Biological characterization of non-steroidal progestins from botanicals used for women's health. Steroids. 2012 Jun;77(7):765-73. Epub 2012 Apr 5. PubMed PMID: 22484153. doi.org/10.1016/j.steroids.2012.03.013
Type: Article
Description: NOTICE: this is the author’s version of a work that was accepted for publication in Steroids. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Steroids, Vol 77, Issue 7, (June 2012). doi.org/10.1016/j.steroids.2012.03.013
URI: http://hdl.handle.net/10027/8396
ISSN: 0039-128X
Sponsor: This work was supported by NIH R21 AT005377-01A1 to (JEB) from the National Center for Complementary and Alternative Medicine (NCCAM) and the Office for Research in Women’s Health. This work was supported by the UIC University Graduate Fellowship (MFT). We appreciate the support from the P50 AT00155 UIC/NIH Center for Botanical Dietary Supplements Research sponsored by the Office of Dietary Supplements.
Date Available in INDIGO: 2012-06-27
 

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