During a screening of multiple Chinese herbs, we found that extracts of this plant have antiestrogenic activities, the mechanism(s) of which we probe in this study using both cellular and in vivo models of estrogen action

During a screening of multiple Chinese herbs, we found that extracts of this plant have antiestrogenic activities, the mechanism(s) of which we probe in this study using both cellular and in vivo models of estrogen action. ECC-1 cells by both the antiestrogen ICI 182 780 and PV extract. Interestingly, PV extract did not appear to directly inhibit estrogen signaling. Rather, we found that its activities were probably related to an ability to function as an aryl hydrocarbon receptor (AHR) agonist in ECC-1 cells. In support of this hypothesis, we noted that PV induced CYP1A1, CYP1B1, and AHR repressor expression in a dose-dependent mannerresponses that were blocked by small interfering RNA treatment to reduce AHR and specific AHR antagonists. Ovariectomized immunodeficient RAG-2/gamma(c) knockout mice implanted with human endometrial xenografts developed implants only when treated with estrogen. Mice treated with estrogen and PV tea in their drinking water had fewer and smaller xenograft implants compared with their estrogen-treated counterparts that drank only water (P< 0.05). Analysis of the resulting implants by immunohistochemistry demonstrated persistent estrogen receptor (ER), but reduced proliferation and CYR61 expression. Mouse uterine tissue weight in PV-treated mice was not different from controls, and cycle fecundity of intact C57 female mice was unaffected by PV tea treatment. PV, or Self-heal, exhibits significant antiestrogenic properties, both in vitro and in Apaziquone vivo. This activity is likely due to the ability of PV-activated AHR to interfere with estrogen. This herb may be useful as an adjunct Apaziquone for the treatment of estrogen-dependent processes like endometriosis and breast and uterine cancers. Full characterization of this herb will likely provide new insights into the crosstalk between AHR and ESR1, with potential for therapeutic applications in women. Keywords:aryl hydrocarbon receptor, cell lines, chinese herbs, endometriosis, endometrium, estradiol, estradiol receptor, female reproductive tract, herbal therapy, implantation A common herbal remedy with significant antiestrogenic activity shows promise for the treatment of endometriosis and other gynecologic disorders that respond to estrogen and may provide a new treatment for infertility. == INTRODUCTION == Estrogens are steroid hormones with a variety of functions in many target tissues. While essential for reproductive function, the effects of estrogen can be detrimental or support abnormal cell growth and/or differentiation. The actions of unopposed estrogen or estrogen in the face of progesterone (P) resistance can promote various gynecologic disorders, including endometriosis, endometrial hyperplasia, and cancer [13]. Understanding the role of estrogen and other sex steroids Rabbit Polyclonal to IL4 will likely lead to an improved understanding of hormone-dependent diseases and their treatments. Estrogen replacement therapy has known risks and side effects that may mitigate its usefulness in menopause. Likewise, endogenous estrogen in women of reproductive age may worsen or aggravate preexisting conditions, such as endometriosis or uterine fibroids [4,5]. Likewise, the use of antiestrogens or medical suppression of estrogen has proven benefit in gynecology [69]. However, in some cases, antiestrogens, such as tamoxifen, that benefit target tissues like those of the breast, have unanticipated adverse effects on the endometrium [10,11]. To this end, pharmaceutical companies have sought to develop selective estrogen receptor modulators (SERMs) that might provide better activity profiles to selectively benefit bone and breast tissues, while not increasing risk of endometrial hyperplasia or cancer and heart disease. Finally, uterine receptivity may be compromised by excess estrogen activity [1215]. Availability Apaziquone of an effective antiestrogen would likely have utility for the treatment of infertility and such defects in uterine receptivity caused by prolonged or exaggerated estrogen action. There is increasing interest in herbal and botanical remedies in gynecology [1619]. For a variety of reasons, many more women are actively seeking natural or nontraditional medicinal approaches to treat a Apaziquone wide variety of complaints and conditions [2022]. Recently, the American College of Obstetrics and Gynecology issued its firstClinical Update in Women’s Healthon the subject of complementary and alternative medicine [23], and the number of publications on gynecologic uses of herbal therapies is rapidly.