alexa Kaempferol Exhibits Progestogenic Effects in Ovariectomized Rats
ISSN: 2157-7536

Journal of Steroids & Hormonal Science
Open Access

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Research Article

Kaempferol Exhibits Progestogenic Effects in Ovariectomized Rats

May Fern Toh, Emma Mendonca, Sharon L. Eddie, Michael P. Endsley, Daniel D. Lantvit, Pavel A. Petukhov, and Joanna E. Burdette*

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60607, USA

*Corresponding Author:
Joanna E. Burdette
900 S. Ashland Street (M/C 870) Chicago, IL 60607, USA
Tel: 312-996-6153
Fax: 312-996-7107
E-mail: [email protected]

Received date: April 15, 2014; Accepted date: June 26, 2014; Published date: July 02, 2014

Citation: Toh MF, Mendonca E, Eddie SL, Endsley MP, Lantvit DD, et al. (2014) Kaempferol Exhibits Progestogenic Effects in Ovariectomized Rats. J Steroids Hormon Sci 5:136. doi:10.4172/2157-7536.1000136

Copyright: © 2014 Toh MF, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Objective: Progesterone (P4) plays a central role in women's health. Synthetic progestins are used clinically in hormone replacement therapy (HRT), oral contraceptives, and for the treatment of endometriosis and infertility. Unfortunately, synthetic progestins are associated with side effects, including cardiovascular disease and breast cancer. Botanical dietary supplements are widely consumed for the alleviation of a variety of gynecological issues, but very few studies have characterized natural compounds in terms of their ability to bind to and activate progesterone receptors (PR). Kaempferol is a flavonoid that functions as a non-steroidal selective progesterone receptor modulator (SPRM) in vitro. This study investigated the molecular and physiological effects of kaempferol in the ovariectomized rat uteri.

Methods: Since genistein is a phytoestrogen that was previously demonstrated to increase uterine weight and proliferation, the ability of kaempferol to block genistein action in the uterus was investigated. Analyses of proliferation, steroid receptor expression, and induction of well-established PR-regulated targets Areg and Hand2 were completed using histological analysis and qPCR gene induction experiments. In addition, kaempferol in silico binding analysis was completed for PR. The activation of estrogen and androgen receptor signalling was determined in vitro.

Results: Molecular docking analysis confirmed that kaempferol adopts poses that are consistent with occupying the ligand-binding pocket of PRA. Kaempferol induced expression of PR regulated transcriptional targets in the ovariectomized rat uteri, including Hand2 and Areg. Consistent with progesterone-like activity, kaempferol attenuated genistein-induced uterine luminal epithelial proliferation without increasing uterine weight. Kaempferol signalled without down regulating PR expression in vitro and in vivo and without activating estrogen and androgen receptors.

Conclusion: Taken together, these data suggest that kaempferol is a unique natural PR modulator that activates PR signaling in vitro and in vivo without triggering PR degradation.

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