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27-Hydroxycholesterol: Molecular Insights into a Pivotal Oxysterol

Endocrinology Diagnostics

Introduction

  • 27-Hydroxycholesterol (27-OHC) is an oxysterol involved in managing cholesterol levels and cell signalling.
  • Examined for its molecular properties and diverse impact on human health and diseases.

Molecular Structure and Biosynthesis

  • Key oxidized derivative of cholesterol with a hydroxyl group at the 27th carbon.
  • Created by the enzyme cholesterol 25-hydroxylase (CH25H).
  • Biosynthetic pathway:
    • Synthesized in the liver and various tissue macrophages.
    • Produced through enzymatic oxidation of cholesterol.
    • Acts as a metabolic intermediate and signalling molecule.
    • Can cross cellular membranes.
  • Key molecular characteristics:
    • Molecular weight: 402.65 g/mol
    • Chemical formula: C27H46O2
    • Lipophilic nature enabling cellular membrane traversal.
    • Modulates multiple cellular signalling pathways.

Physiological Roles and Cellular Interactions

  • Adaptable and significant role in various bodily functions:
    • Lipid Metabolism: Regulates cholesterol homeostasis, Modulates cellular cholesterol efflux mechanisms, Interacts with liver X receptors (LXRs), Crucial for macrophage lipid regulation.
    • Endocrine Signalling: Acts as an endogenous selective estrogen receptor modulator (SERM), Influences estrogen receptor α and β signalling pathways, Interacts with steroid hormone receptors, Implications in reproductive biology and cancer research.
    • Immune System Modulation: Exhibits immunomodulatory properties, Influences macrophage inflammatory responses, Contributes to innate immune system regulation, Role in managing inflammatory conditions.
    • Neurological Implications: Detected in brain tissues, Involved in neuroinflammatory processes, May contribute to neurodegenerative disease mechanisms, Target for neurological research.

Pathological Associations and Clinical Significance

  • Involvement in various pathological conditions:
    • Cancer Biology: Effects on breast cancer cell proliferation, Role in hormone-dependent cancer progression, Influences cell signalling and metastatic potential, Subject of ongoing research.
    • Cardiovascular Diseases: Implicated in atherosclerosis development, Contributes to oxidative stress mechanisms, Potential biomarker for cardiovascular risk assessment, Influences cholesterol efflux and lipid metabolism.
    • Neurodegenerative Disorders: Potential link to Alzheimer's disease pathogenesis, Contributes to neuroinflammatory processes, Target for potential therapeutic interventions, Ongoing neurological research.

Conclusion

  • 27-Hydroxycholesterol is a molecule with intricate connections to cellular functions.

Researchers find it intriguing for its potential impact on health and disease outcomes.

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