Characterization of Phytohormones from Botanical Supplements for Steroid Hormone Receptor Activity

Botanical supplements are popular among consumers even though they are not tightly regulated by the FDA. It is unclear what compounds are in botanical supplements. Previous research has demonstrated that botanical supplements contain steroidal compounds, i.e. phytoestrogens and phytoprogestins. These compounds bind to the estrogen receptor and the progesterone receptor, respectively. Many ligands for the progesterone receptor also bind to the glucocorticoid receptor and the androgen receptor. An example of this is the phytoprogestin, apigenin, which has been found to bind to the androgen receptor, indicating that it is behaving as a phytohormone. We hypothesize that botanicals contain phytohormone compounds that signal through the progesterone and glucocorticoid receptors to impact steroid signaling. Two methods were used to identify phytoprogestin compounds from botanical supplements that are widely used by women: bioassay guided fractionation and structure activity relationships. Using these two methods, two compounds that had activity for the progesterone receptor were identified: baicalein and irilone. This thesis outlines the mechanism of action of baicalein and irilone on steroid hormone receptors. The studies outlined in this thesis demonstrate that botanicals contain compounds that can bind to multiple steroid receptors and that steroid receptor expression is important for their activity. The progestogenic mechanism of action of baicalein and irilone has unearthed important crosstalk between PR and GR that has not been demonstrated before. This could be important for understanding how steroid hormones work together in the reproductive tract and possibly how gynecological diseases can progress. Uncovering baicalein’s and irilone’s progestogenic and glucocorticoid action can lead to potential therapies for gynecological ailments like infertility and prevention of endometrial and ovarian cancer.