Kaempferol Exhibits Progestogenic Effects in Ovariectomized Rats.

Area of Science:

• Endocrinology and Reproductive Biology
• Natural Product Chemistry
• Molecular Pharmacology

Background:

• Progesterone (P4) is crucial for women's health, with synthetic progestins used in various therapies.
• Synthetic progestins carry risks like cardiovascular disease and breast cancer.
• Natural compounds' ability to modulate progesterone receptors (PR) is largely uncharacterized.

Purpose of the Study:

• To investigate the molecular and physiological effects of kaempferol, a flavonoid, in ovariectomized rat uteri.
• To determine if kaempferol acts as a selective progesterone receptor modulator (SPRM).
• To assess kaempferol's ability to block genistein's estrogenic effects in the uterus.

Main Methods:

• In silico molecular docking to analyze kaempferol binding to the progesterone receptor (PR).
• Histological analysis and qPCR to assess uterine proliferation and PR-regulated gene targets (Areg, Hand2).
• In vitro assays to determine activation of estrogen and androgen receptors.

Main Results:

• Kaempferol binds to the PR ligand-binding pocket, consistent with SPRM activity.
• Kaempferol induced PR-regulated genes (Hand2, Areg) in rat uteri.
• Kaempferol attenuated genistein-induced proliferation without increasing uterine weight, and did not activate estrogen or androgen receptors.

Conclusions:

• Kaempferol functions as a unique natural SPRM.
• Kaempferol activates PR signaling in vitro and in vivo.
• Kaempferol offers a potential therapeutic agent without triggering PR degradation or activating other steroid receptors.