Botanical derived progestins and their impact on women's health

植物源孕激素及其对女性健康的影响

• 批准号: 9236152
• 负责人: Joanna E Burdette
• 金额: $ 35.98万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9236152
• 关键词: Affect; Affinity; Agonist; Amphiregulin; Androgen Receptor; Binding; Biological; Biological Assay; Botanical dietary supplements; Botanicals; Breast; Cimicifuga racemosa; Complex Mixtures; Contraceptive methods; Data; Dogwood; Elements; Employee Strikes; Endometrial Carcinoma; Endometrium; Epithelial Cells; Epithelium; Erinaceidae; Estrogens; Fertility; Fibroid Tumor; Fractionation; Gene Expression Regulation; Genetic Transcription; Ginger; Glucocorticoid Receptor; Health; Health Benefit; Hormonal; Hormone replacement therapy; Hormone use; Humulus; Hyperplasia; IGFBP2 gene; Knowledge; Literature; Luciferases; Malignant Neoplasms; Malignant neoplasm of ovary; Mammary gland; Measures; Menopausal Symptom; Messenger RNA; Mission; Modeling; Monitor; Natural Products; Oregano spice; Pathology; Phytoestrogens; Pilot Projects; Plant Extracts; Plants; Prevention; Process; Progesterone; Progesterone Receptors; Progestins; Proteins; Rattus; Receptor Signaling; Regulation; Reporter; Reporting; Research; Risk; Safety; Screening Result; Series; Signal Transduction; Specificity; Stromal Cells; Testing; Tissues; Trifolium pratense; Uterine Cancer; Uterus; Verbena; Woman; Women' s Health; Yam - dietary; base; biomarker panel; birth control; emergency contraception; endometriosis; estrogenic; gene induction; high throughput screening; improved; in vivo; inhibitor/antagonist; malignant breast neoplasm; prevent; progesterone receptor A; public health relevance; receptor; receptor binding; response; virtual

 DESCRIPTION (provided by applicant): Virtually all women will use progesterone as a therapy at some point in their lives; despite this, very little research has been conducted on alternative phytoprogestins available in consumable botanical supplements. The breadth of circumstances that employ progestin-containing therapies is striking: endometriosis, fibroids, menopausal symptoms, contraception, and cancers, in all affect hundreds of millions of women worldwide. Botanical dietary supplements are consumed by millions of women. Our preliminary data suggest that the supplements women are consuming contain phytoprogestins that interact with progesterone receptors and modulate hormonal signaling, which if consumed by women could have an impact on various pathologies such as endometriosis, fibroids, fertility modulation, and prevention and treatment of endometrial cancers. Alternatively, women consuming estrogens should use them in combination with progestins to oppose estrogenic action in the uterus that increases the risk of hyperplasia and cancer. From a diverse panel of plants selected based on a series of in house screening results, studies for women's health benefits in the UIC Botanical Center, and a literature report that screened over 150 traditionally used plants for the presence of phytoprogestins, we will synergize with the mission of the UIC Center and test our hypothesis that progesterone-like compounds are present in botanicals and exert tissue-specific gene induction in the breast and uterus. We will 1) Identify the component(s) responsible for the progesterone-like activity in botanicals and develop a high-throughput screen that allows us to detect and identify them from complex mixtures of natural products, 2) Biologically characterize progestins from botanical extracts in regard to their safety and efficacy by measuring their activation of tissue-specific markers and their specificity for androgen receptors and glucocorticoid receptors, and 3) Elucidate the interaction between phytoprogestins and phytoestrogens on tissue specific gene regulation of the breast and uterus. Since progestins are used for hormone replacement, birth control, emergency contraception, and the treatment of endometriosis, fibroids, and uterine cancer, identifying if and when women are consuming these molecules is critical for their safe and effective use. Women are already exposing themselves to many of these progesterone-like molecules in botanical dietary supplements, and we have no knowledge of where these compounds are present, of their tissue specific effects, or of what their overall impact is on women's health. In order for a woman to safely and effectively use or avoid these compounds, they need to be identified and quantified. This study will provide an important avenue for the identification and characterization of selective natural progesterone compounds from botanical extracts. Therefore, a more focused approach at identifying progestins and characterizing their action - especially from commonly used botanical supplements - is of imminently high impact.

 描述（由申请人提供）：几乎所有的妇女将使用孕酮作为治疗在他们的生活中的某个点;尽管如此，很少有研究已经进行了替代植物孕激素可在消费植物补充剂。使用含孕激素治疗的情况范围是惊人的：子宫内膜异位症，纤维瘤，更年期症状，避孕和癌症，在所有影响全球数亿妇女。数百万妇女食用植物性膳食补充剂。我们的初步数据表明，女性正在食用的补充剂含有植物孕激素，这些植物孕激素与孕激素受体相互作用并调节激素信号，如果女性食用，可能会对各种病理产生影响，如子宫内膜异位症，子宫肌瘤，生育调节以及预防和治疗子宫内膜癌。或者，女性消费雌激素应使用它们与孕激素结合，以对抗雌激素在子宫内的作用，增加增生和癌症的风险。根据一系列内部筛选结果，UIC植物中心对妇女健康益处的研究，以及筛选了150多种传统植物中存在植物孕激素的文献报告，选择了多种植物，我们将与UIC中心的使命协同作用，并测试我们的假设，即植物中存在胆甾酮样化合物，并对组织产生作用-乳腺和子宫中的特定基因诱导。我们将1）鉴定植物中负责甾酮样活性的组分，并开发高通量筛选，使我们能够从天然产物的复杂混合物中检测和鉴定它们，2）从植物提取物中生物学表征孕激素的安全性 通过测量它们对组织特异性标记物的激活和它们对雄激素受体和糖皮质激素受体的特异性，以及3）阐明植物孕激素和植物雌激素对乳腺和子宫的组织特异性基因调节的相互作用。由于孕激素用于激素替代，避孕，紧急避孕以及子宫内膜异位症，纤维瘤和子宫癌的治疗，因此确定女性是否以及何时服用这些分子对于其安全和有效使用至关重要。女性已经在植物膳食补充剂中暴露于许多这些类似于胆固醇的分子，我们不知道这些化合物存在于何处，它们的组织特异性作用，或者它们对女性健康的总体影响。为了让女性安全有效地使用或避免这些化合物，需要对它们进行识别和量化。本研究为从植物提取物中选择性地鉴定和表征天然孕酮化合物提供了重要途径。因此，一个更有针对性的方法来识别孕激素并表征其作用-特别是从常用的植物补充剂-具有迫切的高影响。