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Brandi Smith

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Non-Nuclear Estrogen Receptor Activation Improves Hepatic Steatosis in Female Mice.

Estrogens have the potential to afford atheroprotection, to prevent excess adiposity and its metabolic complications including insulin resistance, and to lessen hepatic steatosis. Cellular responses to estrogens occur through gene regulation by nuclear estrogen receptors (ER), and through signal initiation by plasma membrane-associated ER. Leveraging the potentially favorable cardiometabolic actions of estrogens has been challenging […]

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Estrogen receptor-α and aryl hydrocarbon receptor involvement in the actions of botanical estrogens in target cells.

Botanical estrogen (BE) dietary supplements are consumed by women as substitutes for loss of endogenous estrogens at menopause. To examine the roles of estrogen receptor α (ERα) and aryl hydrocarbon receptor (AhR) and their crosstalk in the actions of BEs, we studied gene regulation and proliferation responses to four widely used BEs, genistein, daidzein, and […]

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ERα-XPO1 crosstalk controls tamoxifen sensitivity in tumors by altering ERK5 cellular localization

Most breast cancer deaths occur in women with recurrent, ERα (+), metastatic tumors. There is a critical need for therapeutic approaches that include novel, targetable mechanism-based strategies by which ERα (+) tumors can be resensitized to endocrine therapies. The objective of this study was to validate a group of nuclear transport genes as potential biomarkers […]

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Estrogen and Microbiota Crosstalk: Should We Pay Attention?

Recent advances have suggested that steroid hormones such as estrogens, and gut microbiota might synergize to influence obesity, diabetes, and cancer. We discuss recent knowledge of the interactions between estrogens and gut microbiota, and new insights that might offer new approaches to influence this crosstalk and improve metabolic outcomes. Link

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Nuclear and extranuclear-initiated estrogen receptor signaling crosstalk and endocrine resistance in breast cancer

Estrogens regulate function of reproductive and non-reproductive tissues in healthy and diseased states including breast cancer. They mainly work through estrogen receptor alpha (ERα) and/or estrogen receptor beta (ERβ). There are various ERα targeting agents that have been used for treatment of ER (+) breast tumors. The impact of direct nuclear activity of ER is […]

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Design of pathway preferential estrogens that provide beneficial metabolic and vascular effects without stimulating reproductive tissues

There is great medical need for estrogens with favorable pharmacological profiles that support desirable activities for menopausal women, such as metabolic and vascular protection, but that lack stimulatory activities on the breast and uterus. We report the development of structurally novel estrogens that preferentially activate a subset of estrogen receptor (ER) signaling pathways and result […]

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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

With the advent of the -omics approaches our understanding of the chronic diseases like cancer and metabolic syndrome has improved. However, effective mining of the information in the large-scale datasets that are obtained from gene expression microarrays, deep sequencing experiments or metabolic profiling is essential to uncover and then effectively target the critical regulators of […]

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Differential Utilization of Nuclear and Extranuclear Receptor Signaling Pathways in the Actions of Estrogens, SERMs, and a Tissue-Selective Estrogen Complex (TSEC)

Estrogens act through nuclear and extranuclear initiated pathways involving estrogen receptors (ERs) to regulate gene expression and activate protein kinases. We investigated the involvement of extracellular signal-regulated kinase2 (ERK2) and ERα in the activities of estradiol (E2), conjugated estrogens (CEs), selective estrogen receptor modulators (SERMs), and a Tissue-Selective Estrogen Complex (TSEC), a combination of a […]

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Dietary licorice root supplementation reduces diet-induced weight gain, lipid deposition, and hepatic steatosis in ovariectomized mice without stimulating reproductive tissues and mammary gland

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