MCF7 cells are an estrogen-responsive human breast cancer cell line that expresses both estrogen receptor (ER) alpha and ERbeta. Treatment of MCF7 cells with artemisinin, an antimalarial phytochemical from the sweet wormwood plant, effectively blocked estrogen-stimulated cell cycle progression induced by either 17beta-estradiol (E(2)), an agonist for both ERs, or by propyl pyrazole triol (PPT), a selective ERalpha agonist. Artemisinin strongly downregulated ERalpha protein and transcripts without altering expression or activity of ERbeta.
Because the prevailing form of hormone replacement therapy is associated with the development of cancer in breast and endometrial tissues, alternatives are needed for the management of menopausal symptoms. Formulations of Trifolium pratense L. (red clover) are being used to alleviate menopause-associated hot flashes but have shown mixed results in clinical trials. The strobiles of Humulus lupulusL.
Macaques provide an important animal model for the study of hormonal agents and their effects on risk biomarkers for breast cancer. A common criticism of this model is that spontaneous breast cancer has rarely been described in these animals. In this report, we characterize 35 mammary gland lesions ranging from ductal hyperplasia to carcinoma in situ and invasive ductal carcinoma in cynomolgus and rhesus macaques. Based on a retrospective analysis, we estimated the lifetime incidence of mammary gland neoplasia in aged female macaques to be about 6%.
Ductal morphogenesis of the mammary gland occurs largely in the early pubertal period under the influence of ovarian sex hormones. In this study we characterized developing ductal structures in breast tissue of 14 female prepubertal or early pubertal rhesus monkeys (average age, 2.6 +/- 0.1 years). Serum estradiol concentrations ranged from < 5.0 to 61.2 pg/ml, while progesterone concentrations were low in all animals (< 0.6 ng/ml). No corpora lutea were seen on ovarian histology.
OBJECTIVE: Outcomes from the Women's Health Initiative have demonstrated adverse effects associated with hormone therapy and have prioritized the need to develop new alternative treatments for the management of menopause and osteoporosis. To this end, we have been investigating natural herbal medicines used by Costa Rican women to manage menopausal symptoms. METHODS: Seventeen plant species were collected and extracted in Costa Rica.
OBJECTIVES: To investigate the biological activities of Justicia pectoralis Jacq. (Acanthaceae), an herbal medicine used in Costa Rica (CR) for the management of menopausal symptoms and dysmenorrhea. STUDY DESIGN: The aerial parts of J. pectoralis were collected, dried and extracted in methanol. To establish possible mechanisms of action of JP for the treatment of menopausal symptoms, the estrogenic and progesterone agonists, and antiinflammatory activities were investigated.
We have previously described diminished uterine progesterone response and increased uterine sensitivity to inflammation in adult female mice with a history of developmental exposure to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). Since parturition in mammals is an inflammatory process mediated in part by a decline in progesterone action, toxicant-mediated disruption of progesterone receptor (PR) expression at the maternal-fetal interface would likely impact the timing of birth.
We have recently reported that adult male C57BL/6 mice exposed in utero to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) confer an increased risk of preterm birth (PTB) to unexposed females. Risk of PTB was coincident with decreased placental progesterone receptor (Pgr) mRNA expression and increased toll-like receptor 4 (Tlr4) mRNA expression, suggesting that toxicant exposure induced a heightened inflammatory response at the maternal-fetal interface.
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 undesirable side effects including cardiovascular diseases and breast cancers. Therefore, identifying alternative progestins is clinically significant.
Obesity is a risk factor for the development of hormone receptor-positive breast cancer in postmenopausal women. Estrogen synthesis is catalyzed by aromatase. Recently, we identified an obesity→inflammation→aromatase axis in mouse models and women. In mouse models of obesity, inflammatory foci characterized by crown-like structures (CLS) consisting of dead adipocytes encircled by macrophages were found in the mammary gland. CLS of the breast were found in most overweight and obese women.