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Estrogen replacement regimen and brain infusion of lipopolysaccharide differentially alter steroid receptor expression in the uterus and hypothalamus

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Abstract

The regimen of estrogen replacement can alter the consequences of estrogen therapy and stressors. To determine the long-term effects and interaction of these systems on the brain and periphery, adult female rats were infused with lipopolysaccharide (LPS) into the fourth ventricle of the brain for 4 weeks, and ovariectomized rats were administered either constant or pulsed regimens of estrogen replacement (17β-estradiol) until sacrifice at 8 weeks. Constant, but not pulsed, estrogen replacement reduced ERα and increased HSP90, HSP70, and PRB uterine protein levels. Both estrogen regimens increased ERβ, HSP27, and PRA uterine proteins. Both regimens reduced hypothalamic levels of ERα, but not ERβ, HSP, or PR. No changes were observed in the hippocampus. Long-term brain infusion of LPS activated microglia and reduced body weight, but did not alter corticosterone or nitrotyrosine levels. LPS infusion into intact rats suppressed uterine weight, increased ERα and decreased HSP90 in the uterus. LPS did not alter uterine weight in ovariectomized rats treated with constant or pulsed estrogen. Together, these data suggest the timing of estrogen replacement and neuroinflammatory stressors can profoundly affect uterine and hypothalamic steroid receptor expression and may be important parameters to consider in the post-menopausal intervention with estrogen.

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Acknowledgments

We would like to thank Drs. Damani N. Bryant, David S. Herman and Yannick Marchalant for their thoughtful critiques of the manuscript. Supported by the U.S. Public Health Service (AG030331, to GLW), the Alzheimer’s Association (IIRG-010-2654, to GLW), NIH (NS20311-23 to DMD) and Reproductive Biology Training Grant (T32-HD007133-27 to LKM).

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Authors and Affiliations

  1. Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, OR, USA

    L. K. Marriott, L. C. Sheldahl, R. A. Shapiro & D. M. Dorsa

  2. Arizona Research Laboratories, Division of Neural Systems, Memory & Aging, University of Arizona, Tucson, AZ, USA

    K. R. McGann-Gramling & B. Hauss-Wegrzyniak

  3. Departments of Psychology & Neuroscience and Molecular, Virology, Immunology & Medical Genetics, Ohio State University, 1885 Neil Avenue, Columbus, OH, 43210, USA

    G. L. Wenk

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  1. L. K. Marriott
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Marriott, L.K., McGann-Gramling, K.R., Hauss-Wegrzyniak, B. et al. Estrogen replacement regimen and brain infusion of lipopolysaccharide differentially alter steroid receptor expression in the uterus and hypothalamus. Endocr 32, 317–328 (2007). https://doi.org/10.1007/s12020-008-9038-1

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