Cholesterol homeostasis is tightly regulated by a group of endocrine hormones under physiological conditions. Hormonal dysregulation is often associated with disturbed cholesterol homeostasis, resulting in many clinical disorders including atherosclerosis, fatty liver and metabolic syndrome. Circulating hormones regulate cholesterol metabolism by altering levels of relative genes either through their interactions with nuclear receptors or by interfering with bile acid signaling pathways. A better understanding of hormonal regulation of cholesterol metabolism would improve our likelihood of identifying effective and selective targets for the intervention of disturbed cholesterol. In this review, we discuss selected hormones critical for the cholesterol balance, including thyroid hormone, sex hormones, growth hormone, glucagon and irisin. We focus our discussion on the most recent advance in clinical epidemiology, animal mechanistic studies and the clinical application.
""What is this cholesterol?"" In this book entitled ""Cholesterol- Good, Bad, and the Heart"" now you got the answers given by the experts in the field. Moreover, you can explore more by reading the references/citations given in the articles of each chapter. It is still an emerging field and lot more is being discovered. You will be amazed how much knowledge is already there in this book on cholesterol. You will realize that cholesterol is an essential and extremely important building block of cell membranes and thus serves vital functions in the body. I believe this book will be incredibly powerful and useful in teaching to give new perspectives on cholesterol.
An intimate relation between hormones and lipoprotein metabolism has been known for a long time especially from hormone-deficiency or -overproduction syndromes. The mechanisms through which hormones influence lipid metabolism have become a field of major interest in sci ence. The more we learn about cellular hormonal actions the better we understand regulatory processes and phenomena occuring in patients. The present book summarizes data discussed at an International Meet ing at Marburg, Germany, on "Hormones in Lipoprotein Metabolism". It was an attempt to pull together knowledge in basic science from the mode of action of hormones all the way to clinical appearance of hor monal disorders involving lipoprotein metabolism. Thus data on molec ular biology, on hormonal regulation of apolipoprotein synthesis, on lipoprotein receptors and enzyme induction are discussed together with the large field of oral contraceptive use, postmenopausal estrogen sub stitution, lipid disorders in diabetes mellitus, in thyroid dysfunction, in adrenal insufficiency and in glucocorticoid application. We are aware of the fact that such an overview cannot be complete but should serve as a collection of data and ideas for those interested in hormonal regulation of lipid metabolism. We thank all authors for taking an extra effort in writing up their presentations and thus making this edition possible. We also thank Bristol-Myers-Squibb for generous support of the meeting and of the final publication. Marburg, Germany ARMIN STEINMETZ JURGEN SCHNEIDER HANS KAFFARNIK Contents Molecular Biology Chairmen: D. J. Rader, A.
Cholesterol is an essential cellular lipid that is a regulator of membrane organization and fluidity, and is an obligate precursor for synthesis of steroid hormones, oxysterols and bile acids. Cellular cholesterol homeostasis is tightly regulated through a network of transcriptional and non-transcriptional pathways. To further delineate intracellular cholesterol trafficking pathways, we initiated a loss-of-function genetic screen in Chinese hamster ovary cells (CHO), selecting for CHO mutants with altered cholesterol trafficking. Here we characterize one of the isolated mutants in which the locus encoding small nucleolar RNA hosting gene 3 (SNHG3) is disrupted. Altered cholesterol trafficking phenotype is not due to reduced expression of the SNHG3 mRNA, but rather results from haploinsufficiency of the H/ACA small nucleolar RNA (snoRNA) U17, a small non-coding RNA produced from the hosting gene SNHG3 introns. Previously identified function of U17 snoRNA is to mediate 18S rRNA processing, yet cells haploinsufficient for U17 show normal maturation and amount of 18S rRNA, indicating that altered cholesterol trafficking is not caused by defects in rRNA processing. Through expression profiling, we identify that mRNA of mitochondrial adapter protein HUMMR is a target that is negatively regulated by U17 snoRNA. HUMMR mRNA is up-regulated U17 snoRNA-deficient cells and down-regulated in U17 snoRNA-overexpression cells. Up-regulation of HUMMR itself is sufficient to alter cholesterol trafficking, suggesting HUMMR functions downstream of U17 snoRNA-initiated regulation of cholesterol homeostasis. We show that up-regulation of HUMMR protein in U17 snoRNA-deficient cells promotes formation of ER-mitochondrial contacts, decreasing esterification of cholesterol and facilitating cholesterol trafficking to mitochondria, which increases the synthesis of 27-hydroxy cholesterol and pregnenolone in mitochondria. We also show that levels of U17 snoRNA and HUMMR are developmentally regulated in steroidogenic tissues. As HUMMR level increases in maturing ovarian tissue, expression of U17 snoRNA gradually decreases. This suggests negative regulation of HUMMR by U17 snoRNA in vivo that may be critical for regulation of steroidogenesis. Together, this dissertation describes U17 snoRNA as a new class of non-coding RNA that modulates cholesterol trafficking by regulating downstream coding genes. U17 snoRNA and HUMMR regulate mitochondrial synthesis of steroids, and are developmentally regulated in steroidogenic tissues, suggesting that the U17 snoRNA-HUMMR pathway may serve a previously unrecognized, physiological role in gonadal tissue maturation and steroidogenesis.
The Biology of Cholesterol and Related Steroids focuses on the study of sterols in relation to living organisms. The publication first takes a look at the analysis of sterols and related steroids and the distribution of sterols and related steroids in nature, as well as the processes of extraction and separation and presence of sterols in plants, fungi, vertebrates, and invertebrates. The text then ponders on biosynthesis of sterols and metabolism of cholesterol. Topics include formation of fatty acid esters of cholesterol, steroid hormones, biosynthetic pathway to sterols, reaction mechanisms, and comparative aspects of sterol synthesis. The manuscript examines the developmental aspects of cholesterol metabolism and sterols in biological membranes. The book also reviews cholesterol synthesis in animal tissues, sterol metabolism in isolated cells, and epidemiology of the plasma cholesterol. Discussions focus on selection of statistical populations, genetic influences, regulation of sterol synthesis, general aspects of sterol metabolism, and removal of cell cholesterol in vivo. The publication is a dependable source of data for biochemists and readers interested in the biology of cholesterol and steroids.
This volume provides state-of-the-art techniques for studying various aspects of cholesterol homeostasis, including its uptake, synthesis and efflux from the cell, as well as its trafficking within the cell. Chapters also cover techniques for studying the regulation of cholesterol homeostasis at both the transcriptional and post-translational levels, as well as studying the membrane topology and structure of cholesterol-related proteins. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Cholesterol Homeostasis: Methods and Protocols aims to provide key techniques in tackling the investigation of cholesterol homeostasis.
