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      Metabolic profiling of cholesterol and sex steroid hormones to monitor urological diseases

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          Abstract

          Cholesterol and sex steroid hormones including androgens and estrogens play a critical role in the development and progression of urological diseases such as prostate cancer. This disease remains the most commonly diagnosed malignant tumor in men and is the leading cause of death from different cancers. Attempts to understand the role of cholesterol and steroid metabolism in urological diseases have been ongoing for many years, but despite this, our mechanistic and translational understanding remains elusive. In order to further evaluate the problem, we have taken an interest in metabolomics; a discipline dedicated to the systematic study of biologically active metabolites in cells, tissues, hair and biofluids. Recently, we provided evidence that a quantitative measurement of cholesterol and sex steroid metabolites can be successfully achieved using hair of human and mouse models. The overall goal of this short review article is to introduce current metabolomic technologies for the quantitative biomarker assay development and also to provide new insight into understanding the underlying mechanisms that trigger the pathological condition. Furthermore, this review will place a particular emphasis on how to prepare biospecimens (e.g., hair fiber), quantify molecular profiles and assess their clinical significance in various urological diseases.

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          Most cited references91

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          Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones.

          Significant advances have taken place in our knowledge of the enzymes involved in steroid hormone biosynthesis since the last comprehensive review in 1988. Major developments include the cloning, identification, and characterization of multiple isoforms of 3beta-hydroxysteroid dehydrogenase, which play a critical role in the biosynthesis of all steroid hormones and 17beta-hydroxysteroid dehydrogenase where specific isoforms are essential for the final step in active steroid hormone biosynthesis. Advances have taken place in our understanding of the unique manner that determines tissue-specific expression of P450aromatase through the utilization of alternative promoters. In recent years, evidence has been obtained for the expression of steroidogenic enzymes in the nervous system and in cardiac tissue, indicating that these tissues may be involved in the biosynthesis of steroid hormones acting in an autocrine or paracrine manner. This review presents a detailed description of the enzymes involved in the biosynthesis of active steroid hormones, with emphasis on the human and mouse enzymes and their expression in gonads, adrenal glands, and placenta.
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            Role of cholesterol and lipid organization in disease.

            Membrane lipids are essential for biological functions ranging from membrane trafficking to signal transduction. The composition of lipid membranes influences their organization and properties, so it is not surprising that disorders in lipid metabolism and transport have a role in human disease. Significant recent progress has enhanced our understanding of the molecular and cellular basis of lipid-associated disorders such as Tangier disease, Niemann-Pick disease type C and atherosclerosis. These insights have also led to improved understanding of normal physiology.
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              Statins and cancer prevention.

              Randomized controlled trials for preventing cardiovascular disease indicated that statins had provocative and unexpected benefits for reducing colorectal cancer and melanoma. These findings have led to the intensive study of statins in cancer prevention, including recent, large population-based studies showing statin-associated reductions in overall, colorectal and prostate cancer. Understanding the complex cellular effects (for example, on angiogenesis and inflammation) and the underlying molecular mechanisms of statins (for example, 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase-dependent processes that involve geranylgeranylation of Rho proteins, and HMG-CoA-independent processes that involve lymphocyte-function-associated antigen 1) will advance the development of molecularly targeted agents for preventing cancer. This understanding might also help the development of drugs for other ageing-related diseases with interrelated molecular pathways.

                Author and article information

                Journal
                Endocr Relat Cancer
                Endocr. Relat. Cancer
                ERC
                Endocrine-Related Cancer
                Bioscientifica Ltd (Bristol )
                1351-0088
                1479-6821
                October 2016
                01 October 2016
                : 23
                : 10
                : R455-R467
                Affiliations
                [1 ]Molecular Recognition Research Center Korea Institute of Science and Technology, Seoul, Korea
                [2 ]Departments of Surgery and Biomedical Sciences Cedars-Sinai Medical Center, Los Angeles, California, USA
                [3 ]Department of Medicine University of California, Los Angeles, California, USA
                Author notes
                Correspondence should be addressed to M H Choi or J Kim; Email: mh_choi@ 123456kist.re.kr or Jayoung.Kim@ 123456cshs.org
                Article
                ERC160285
                10.1530/ERC-16-0285
                5064754
                27580660
                214d9175-4ae8-4a5b-af00-b825fa00cda1
                © 2016 Society for Endocrinology

                This work is licensed under a Creative Commons Attribution 3.0 Unported License

                History
                : 29 July 2016
                : 4 August 2016
                Categories
                Review

                Oncology & Radiotherapy
                steroid,cholesterol,biomarkers,mass spectrometry,metabolomics,urological cancers,prostate diseases

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