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: 9905486
• 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 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9905486
• 关键词: Affect; Affinity; Agonist; Amphiregulin; Androgen Receptor; Binding; Biological; Biological Assay; Botanical dietary supplements; Botanicals; Breast; Cimicifuga racemosa; Complex Mixtures; Consumption; Contraceptive methods; Data; Dogwood; Elements; Endometrial Carcinoma; Endometrium; Epithelial; Epithelial Cells; Epithelium; Erinaceidae; Estrogens; Fertility; Fibroid Tumor; Fractionation; Gene Expression Regulation; Genetic Transcription; Ginger; Glucocorticoid Receptor; Health; Health Benefit; 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; Uterine Fibroids; Uterus; Verbena; Woman; Women' s Health; Yam - dietary; base; biomarker panel; birth control; emergency contraception; endometriosis; estrogenic; gene induction; high throughput screening; hormonal signals; improved; in vivo; inhibitor/antagonist; malignant breast neoplasm; prevent; progesterone receptor A; public health relevance; receptor; receptor binding; response; uterus hyperplasia; 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(申请人提供)：几乎所有的女性都会在她们生命中的某个阶段使用黄体酮作为一种治疗方法；尽管如此，对消耗性植物补充剂中可用的替代植物孕激素的研究很少。使用含有孕激素的疗法的情况是惊人的：子宫内膜异位症、子宫肌瘤、更年期症状、避孕和癌症，总共影响着全球数亿女性。数以百万计的女性食用植物性膳食补充剂。我们的初步数据表明，女性正在摄入的补充剂含有与孕激素受体相互作用并调节激素信号的植孕素，如果女性摄入这些补充剂，可能会对子宫内膜异位症、子宫肌瘤、生育调节以及预防和治疗子宫内膜癌等各种病理产生影响。或者，服用雌激素的女性应该将它们与孕激素联合使用，以反对子宫中的雌激素作用，因为这会增加增殖和癌症的风险。根据一系列内部筛选结果、UIC植物中心对女性健康益处的研究以及一份文献报告(对150多种传统使用的植物进行植物孕激素筛选)，我们将与UIC中心的使命协同工作，验证我们的假设，即植物中存在孕酮类化合物，并在乳房和子宫中进行组织特异性基因诱导。我们将1)确定负责植物中孕酮样活性的成分(S)，并开发一种高通量筛选，使我们能够从天然产品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地表征孕激素的安全性 通过测量组织特异性标志物的激活及其对雄激素受体和糖皮质激素受体的特异性，以及3)阐明植孕素和植物雌激素在乳腺和子宫组织特异性基因调控中的相互作用。由于孕激素用于激素替代、节育、紧急避孕以及治疗子宫内膜异位症、子宫肌瘤和子宫癌，因此确定女性是否以及何时摄入这些分子对于安全有效地使用它们至关重要。女性已经暴露在植物性膳食补充剂中的许多类似黄体酮的分子中，我们不知道这些化合物存在于哪里，它们对组织的特定影响，或者它们对女性健康的总体影响。为了让妇女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。本研究将为从植物提取物中鉴定和鉴定具有选择性的天然孕酮化合物提供重要途径。因此，一种更有针对性的方法来识别孕激素并表征它们的作用--特别是从常用的植物补充剂中--具有迫在眉睫的高影响。