The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis
Abstract Obesity and elevated serum lipids are associated with a threefold increase in the risk of developing atherosclerosis, a condition that underlies stroke, myocardial infarction, and sudden cardiac death. Strategies that aim to reduce serum cholesterol through modulation of liver enzymes have...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-11-01
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| Series: | Biology of Sex Differences |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13293-019-0265-3 |
| _version_ | 1811327346720899072 |
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| author | Taylor Phelps Erin Snyder Erin Rodriguez Hailey Child Pamela Harvey |
| author_facet | Taylor Phelps Erin Snyder Erin Rodriguez Hailey Child Pamela Harvey |
| author_sort | Taylor Phelps |
| collection | DOAJ |
| description | Abstract Obesity and elevated serum lipids are associated with a threefold increase in the risk of developing atherosclerosis, a condition that underlies stroke, myocardial infarction, and sudden cardiac death. Strategies that aim to reduce serum cholesterol through modulation of liver enzymes have been successful in decreasing the risk of developing atherosclerosis and reducing mortality. Statins, which inhibit cholesterol biosynthesis in the liver, are considered among the most successful compounds developed for the treatment of cardiovascular disease. However, recent debate surrounding their effectiveness and safety prompts consideration of alternative cholesterol-lowering therapies, including increasing cholesterol catabolism through bile acid (BA) synthesis. Targeting the enzymes that convert cholesterol to BAs represents a promising alternative to other cholesterol-lowering approaches that treat atherosclerosis as well as fatty liver diseases and diabetes mellitus. Compounds that modify the activity of these pathways have been developed; however, there remains a lack of consideration of biological sex. This is necessary in light of strong evidence for sexual dimorphisms not only in the incidence and progression of the diseases they influence but also in the expression and activity of the proteins affected and in the manner in which men and women respond to drugs that modify lipid handling in the liver. A thorough understanding of the enzymes involved in cholesterol catabolism and modulation by biological sex is necessary to maximize their therapeutic potential. |
| first_indexed | 2024-04-13T15:05:02Z |
| format | Article |
| id | doaj.art-f6bd86b0ad1f424a999b26b776a6ba45 |
| institution | Directory Open Access Journal |
| issn | 2042-6410 |
| language | English |
| last_indexed | 2024-04-13T15:05:02Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj.art-f6bd86b0ad1f424a999b26b776a6ba452022-12-22T02:42:11ZengBMCBiology of Sex Differences2042-64102019-11-0110111210.1186/s13293-019-0265-3The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasisTaylor Phelps0Erin Snyder1Erin Rodriguez2Hailey Child3Pamela Harvey4Department of Molecular, Cellular, and Developmental Biology, University of Colorado at BoulderDepartment of Molecular, Cellular, and Developmental Biology, University of Colorado at BoulderDepartment of Molecular, Cellular, and Developmental Biology, University of Colorado at BoulderDepartment of Molecular, Cellular, and Developmental Biology, University of Colorado at BoulderDepartment of Molecular, Cellular, and Developmental Biology, University of Colorado at BoulderAbstract Obesity and elevated serum lipids are associated with a threefold increase in the risk of developing atherosclerosis, a condition that underlies stroke, myocardial infarction, and sudden cardiac death. Strategies that aim to reduce serum cholesterol through modulation of liver enzymes have been successful in decreasing the risk of developing atherosclerosis and reducing mortality. Statins, which inhibit cholesterol biosynthesis in the liver, are considered among the most successful compounds developed for the treatment of cardiovascular disease. However, recent debate surrounding their effectiveness and safety prompts consideration of alternative cholesterol-lowering therapies, including increasing cholesterol catabolism through bile acid (BA) synthesis. Targeting the enzymes that convert cholesterol to BAs represents a promising alternative to other cholesterol-lowering approaches that treat atherosclerosis as well as fatty liver diseases and diabetes mellitus. Compounds that modify the activity of these pathways have been developed; however, there remains a lack of consideration of biological sex. This is necessary in light of strong evidence for sexual dimorphisms not only in the incidence and progression of the diseases they influence but also in the expression and activity of the proteins affected and in the manner in which men and women respond to drugs that modify lipid handling in the liver. A thorough understanding of the enzymes involved in cholesterol catabolism and modulation by biological sex is necessary to maximize their therapeutic potential.http://link.springer.com/article/10.1186/s13293-019-0265-3BileCholesterolNuclear receptorsEstrogenHormonesCytochrome P450 |
| spellingShingle | Taylor Phelps Erin Snyder Erin Rodriguez Hailey Child Pamela Harvey The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis Biology of Sex Differences Bile Cholesterol Nuclear receptors Estrogen Hormones Cytochrome P450 |
| title | The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis |
| title_full | The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis |
| title_fullStr | The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis |
| title_full_unstemmed | The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis |
| title_short | The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis |
| title_sort | influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis |
| topic | Bile Cholesterol Nuclear receptors Estrogen Hormones Cytochrome P450 |
| url | http://link.springer.com/article/10.1186/s13293-019-0265-3 |
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