Home / Biochemistry / Structural insights into estrogen receptors and antiestrogen therapies

Structural insights into estrogen receptors and antiestrogen therapies

 

Table Of Contents


Chapter ONE

1.1 Introduction
1.2 Background of Study
1.3 Problem Statement
1.4 Objective of Study
1.5 Limitation of Study
1.6 Scope of Study
1.7 Significance of Study
1.8 Structure of the Research
1.9 Definition of Terms

Chapter TWO

2.1 Overview of Estrogen Receptors
2.2 Historical Perspectives on Estrogen Receptors
2.3 Types of Estrogen Receptors
2.4 Functions of Estrogen Receptors
2.5 Estrogen Receptor Modulators
2.6 Antiestrogen Therapies
2.7 Mechanisms of Antiestrogen Therapies
2.8 Efficacy and Side Effects of Antiestrogen Therapies
2.9 Current Research Trends in Antiestrogen Therapies
2.10 Future Directions in Antiestrogen Therapies

Chapter THREE

3.1 Research Design and Methodology
3.2 Selection of Research Participants
3.3 Data Collection Methods
3.4 Data Analysis Techniques
3.5 Ethical Considerations
3.6 Validity and Reliability
3.7 Limitations of the Research Methodology
3.8 Research Tools and Instruments

Chapter FOUR

4.1 Overview of Research Findings
4.2 Analysis of Data
4.3 Comparison of Results with Existing Literature
4.4 Interpretation of Findings
4.5 Discussion on Implications of Findings
4.6 Strengths and Weaknesses of the Study
4.7 Recommendations for Future Research
4.8 Practical Applications of Research Findings

Chapter FIVE

5.1 Summary of Research
5.2 Conclusions
5.3 Contributions to the Field
5.4 Implications for Practice
5.5 Recommendations for Further Studies
5.6 Conclusion Statement

Thesis Abstract

The differential impact of distinct antiestrogens (AEs) is the result of varying structural perturbations they confer to estrogen receptors (ERs) when these small-molecule synthetic compounds compete with endogenous hormones, such as 17β-estradiol. These structural changes translate to altered ability of ERs to conscript cofactors and consequently alter the transcription of their target genes. AEs, depending on the mechanism of action, are classified as either selective estrogen receptor modulators (SERMs), which display tamoxifen-like partial agonism, or as selective estrogen receptor downregulators (SERDs) that confer structurally induced posttranslational modifications (PTMs) that destine these receptors for proteosomal degradation. The conformational plasticity of the ER helix 12 (H12) and how its dynamics and conformational sampling is altered by different AEs are crucial to cofactor recruitment and selectivity, translating to varying degrees of receptor modulation and downstream functional effects. Dissecting these conformational state fluctuations within the context of variable cofactor profiles in different tissues, PTM induction, and emergence of hormonal treatment-related resistance mutations in ERs could lead to improved design of novel therapeutic molecules for breast cancer.

Thesis Overview

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