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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 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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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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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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Integrative Genomics of Gene and Metabolic Regulation by Estrogen Receptors α and β and Coregulators, Madak-Erdogan Z, Charn T.H, Jiang Y, Liu E.T., Katzenellenbogen J.A., Katzenellenbogen B.S.Molecular Systems Biology 2013 Jun 18;9:676,

The closely related transcription factors (TFs), estrogen receptors ERα and ERβ, regulate divergent gene expression programs and proliferative outcomes in breast cancer. Utilizing breast cancer cells with ERα, ERβ, or both receptors as a model system to define the basis for differing response specification by related TFs, we show that these TFs and their key […]

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Non-nuclear Estrogen Receptor α Signaling Promotes Cardiovascular Protection but not Uterine or Breast Cancer Growth in Mice,Chambliss K.L, Wu Q., Oltmann S, Umetani M, Korach K.L., Thomas G.D., Mineo C., Yuhanna I.S., Kim S.H., Madak-Erdogan Z., Maggi A., Dineen S.P., Roland C.L., Brekken R.A., Katzenellenbogen J.A., Katzenellenbogen B.S., Shaul P.W., Journal of Clinical Investigation, 2010,120(7):2319:2330

Steroid hormone receptors function classically in the nucleus as transcription factors. However, recent data indicate that there are also non-nuclear subpopulations of steroid hormone receptors, including estrogen receptors (ERs), that mediate membrane-initiated signaling of unclear basis and significance. Here we have shown that an estrogen-dendrimer conjugate (EDC) that is excluded from the nucleus stimulates endothelial […]

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