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      Tissue-Specific Effects of Loss of Estrogen during Menopause and Aging

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          The roles of estrogens have been best studied in the breast, breast cancers, and in the female reproductive tract. However, estrogens have important functions in almost every tissue in the body. Recent clinical trials such as the Women’s Health Initiative have highlighted both the importance of estrogens and how little we know about the molecular mechanism of estrogens in these other tissues. In this review, we illustrate the diverse functions of estrogens in the bone, adipose tissue, skin, hair, brain, skeletal muscle and cardiovascular system, and how the loss of estrogens during aging affects these tissues. Early transcriptional targets of estrogen are reviewed in each tissue. We also describe the tissue-specific effects of selective estrogen receptor modulators (SERMs) used for the treatment of breast cancers and postmenopausal symptoms.

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          Most cited references 184

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          Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

          The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
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            Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database.

            The past decade has witnessed hundreds of reports declaring or refuting genetic association with putative Alzheimer disease susceptibility genes. This wealth of information has become increasingly difficult to follow, much less interpret. We have created a publicly available, continuously updated database that comprehensively catalogs all genetic association studies in the field of Alzheimer disease (http://www.alzgene.org). We performed systematic meta-analyses for each polymorphism with available genotype data in at least three case-control samples. In addition to identifying the epsilon4 allele of APOE and related effects, we pinpointed over a dozen potential Alzheimer disease susceptibility genes (ACE, CHRNB2, CST3, ESR1, GAPDHS, IDE, MTHFR, NCSTN, PRNP, PSEN1, TF, TFAM and TNF) with statistically significant allelic summary odds ratios (ranging from 1.11-1.38 for risk alleles and 0.92-0.67 for protective alleles). Our database provides a powerful tool for deciphering the genetics of Alzheimer disease, and it serves as a potential model for tracking the most viable gene candidates in other genetically complex diseases.
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              The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994.

              The metabolic syndrome is an important cluster of coronary heart disease risk factors with common insulin resistance. The extent to which the metabolic syndrome is associated with demographic and potentially modifiable lifestyle factors in the US population is unknown. Metabolic syndrome-associated factors and prevalence, as defined by Adult Treatment Panel III criteria, were evaluated in a representative US sample of 3305 black, 3477 Mexican American, and 5581 white men and nonpregnant or lactating women aged 20 years and older who participated in the cross-sectional Third National Health and Nutrition Examination Survey. The metabolic syndrome was present in 22.8% and 22.6% of US men and women, respectively (P =.86). The age-specific prevalence was highest in Mexican Americans and lowest in blacks of both sexes. Ethnic differences persisted even after adjusting for age, body mass index, and socioeconomic status. The metabolic syndrome was present in 4.6%, 22.4%, and 59.6% of normal-weight, overweight, and obese men, respectively, and a similar distribution was observed in women. Older age, postmenopausal status, Mexican American ethnicity, higher body mass index, current smoking, low household income, high carbohydrate intake, no alcohol consumption, and physical inactivity were associated with increased odds of the metabolic syndrome. The metabolic syndrome is present in more than 20% of the US adult population; varies substantially by ethnicity even after adjusting for body mass index, age, socioeconomic status, and other predictor variables; and is associated with several potentially modifiable lifestyle factors. Identification and clinical management of this high-risk group is an important aspect of coronary heart disease prevention.

                Author and article information

                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrin.
                Frontiers in Endocrinology
                Frontiers Research Foundation
                08 February 2012
                : 3
                1Orthopaedic Hospital Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine, University of California Los Angeles Los Angeles, CA, USA
                2Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles Los Angeles, CA, USA
                Author notes

                Edited by: Marc R. Blackman, National Institute of Health, USA

                Reviewed by: David George Monroe, Mayo Clinic College of Medicine, USA; Sarianna Sipila, University of Jyväskylä, Finland

                *Correspondence: Susan A. Krum, Orthopaedic Hospital Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine, University of California Los Angeles, 615 Charles E. Young Dr. South, OHRC 410, Los Angeles, CA 90095, USA. e-mail: skrum@ 123456mednet.ucla.edu

                This article was submitted to Frontiers in Endocrinology of Aging, a specialty of Frontiers in Endocrinology.

                Copyright © 2012 Wend, Wend and Krum.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 190, Pages: 14, Words: 14990
                Review Article

                Endocrinology & Diabetes

                estrogen, serm, aging, tissue specificity


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