Publications

Tissue-Specific Regulation of Genes by Estrogen Receptors

Estrogens are frequently used in reproductive medicine. The Women's Health Initiative trial found that the risks of menopausal hormone therapy (MHT) exceed the benefits. The estrogens in MHT, however, were introduced prior to our understanding of the mechanism of action of estrogens.

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ESTROGEN RECEPTOR β BINDS TO AND REGULATES THREE DISTINCT CLASSES OF TARGET GENES

Estrogen receptorβ (ERβ) has potent antiproliferative and anti-inflammatory properties, suggesting that ERβ-selective agonists might be a new class of therapeutic and chemopreventative agents. To understand how ERβ regulates genes, we identified genes regulated by the unliganded and liganded forms of ERα and ERβ in U2OS cells.

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Estrogen Receptor β-Selective Agonists Stimulate Calcium Oscillations in Human and Mouse Embryonic Stem Cell-Derived Neurons

Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER) in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are postmitotic.

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Estrogen Receptor β Inhibits Human Breast Cancer Cell Proliferation and Tumor Formation by Causing a G2 Cell Cycle Arrest

Studies indicate that estrogen receptor (ER) α mediates breast cancer promotingeffects of estrogens. The role of ERβ in breast cancer is unknown. Elucidating the role of ERβ in the pathogenesis of breast cancer is important because many human breast tumors express both ERα and ERβ.

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Distinct Roles of Unliganded and Liganded Estrogen Receptors in Transcriptional Repression

The decline in estrogen levels during menopause is associated with increased cytokine production and inflammatory diseases. Estrogens exert anti-inflammatory effects by repressing cytokine genes, such as tumor necrosis factor-α (TNFα).

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Differential Regulation of Native Estrogen Receptor- Regulatory Elements by Estradiol, Tamoxifen, and Raloxifene

Estrogen receptors (ERs) regulate gene transcription by interacting with regulatory elements. Most information regarding how ER activates genes has come from studies using a small set of target genes or simple consensus sequences such as estrogen response element, activator protein 1, and Sp1 elements.

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Differential regulation of Native Estrogen Receptor Regulatory Elements by Estradiol, Tamoxifen, and Raloxifene

Estrogen receptors (ER) regulate gene transcription by interacting with regulatory elements. Most information regarding how ER activates genes has come from studies using a small set of target genes or simple consensus sequences such as ERE, AP-1 and Sp1 elements. However, these elements cannot explain the differences in gene regulation patterns and clinical effects observed with E2 and SERMs.

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Drug and Cell Type-Specific Regulation of Genes with Different Classes of Estrogen Receptor β-Selective Agonists

Estrogens produce biological effects by interacting with two estrogen receptors, ERα and ERβ. Drugs that selectively target ERα or ERβ might be safer for conditions that have been traditionally treated with non-selective estrogens. Several synthetic and natural ERβ-selective compounds have been identified.

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Estrogenic Plant Extracts Reverse Weight Gain and Fat

Long-term estrogen deficiency increases the risk of obesity, diabetes and metabolic syndrome in postmenopausal women.
Menopausal hormone therapy containing estrogens might prevent these conditions, but its prolonged use increases the
risk of breast cancer, as wells as endometrial cancer if used without progestins.

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Estradiol and Selective Estrogen Receptor Modulators

Estrogens and selective estrogen receptor modulators (SERMs) interact with estrogen receptor (ER) α and β to activate or
repress gene transcription. To understand how estrogens and SERMs exert tissue-specific effects, we performed microarray
analysis to determine whether ERα or ERβ regulate different target genes in response to estrogens and SERMs. We
prepared human U2OS osteosarcoma cells that are stably transfected with a tetracycline-inducible vector to express ERα or ERβ.

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Liquiritigenin is a plant-derived highly selective estrogen receptor

After the Women's Health Initiative found that the risks of hormone therapy outweighed the benefits,
a need for alternative drugs to treat menopausal symptoms has emerged. We explored the possibility
that botanical agents used in Traditional Chinese Medicine for menopausal symptoms contain ERβ-
selective estrogens. We previously reported that an extract containing 22 herbs, MF101 has ERβ-
selective properties.

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MF101: a multi-component botanical selective estrogen receptor beta modulator for the treatment of menopausal vasomotor symptoms

The Women's Health Initiative Estrogen Plus Progestin clinical
trial demonstrated the risks exceeded the benefits which have led to a decline
in menopausal hormone therapy (MHT) by greater than 50 percent. MHT use was
initiated long before there was a significant understanding of the molecular
mechanisms of estrogens. It has become clear that the problem with the current
estrogens in MHT is they act non-selectively as an agonist in all tissues
that contain estrogen receptors.

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Cell type- and estrogen receptor-subtype specific regulation of selective

Selective estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene can act as estrogen
receptor (ER) antagonists or agonists depending on the cell type. The antagonistic action of tamoxifen
has been invaluable for treating breast cancer, whereas the agonist activity of SERMs also has important
clinical applications as demonstrated by the use of raloxifene for osteoporosis.

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