Sandbox Reserved 490: Difference between revisions
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The genomic mechanism of action occurs within the nucleus of the cell and can be either ligand-dependent or independent. The ligand-dependent mechanism requires the estrogen ligand to diffuse into the cell and then into the nucleus, bind to the LBD of the ER, and induce a conformational change in the receptor protein. The receptor protein then recruits specific co-factors and molecules and assembles a DNA-binding complex, which binds to specific DNA promoter or repressor sequences, depending on the type of cell. | The genomic mechanism of action occurs within the nucleus of the cell and can be either ligand-dependent or independent. The ligand-dependent mechanism requires the estrogen ligand to diffuse into the cell and then into the nucleus, bind to the LBD of the ER, and induce a conformational change in the receptor protein. The receptor protein then recruits specific co-factors and molecules and assembles a DNA-binding complex, which binds to specific DNA promoter or repressor sequences, depending on the type of cell. | ||
Ligand-independent action of the ER occurs when some factor (for example, growth factor) induces a kinase cascade that ultimately phosphorylates the ER and induces the protein to dimerize and act upon DNA and gene transcription. | Ligand-independent action of the ER occurs when some factor (for example, a growth factor) induces a kinase cascade that ultimately phosphorylates the ER and induces the protein to dimerize and act upon DNA and gene transcription. | ||
The ER may act as a transcription factor itself, or it may enhance the activity of other transcription factors. For example, ER has been shown to influence the activity of NFKb in transcribing interleukin-6. These genomic mechanisms are relatively slow. | The ER may act as a transcription factor itself, or it may enhance the activity of other transcription factors. For example, ER has been shown to influence the activity of NFKb in transcribing interleukin-6. These genomic mechanisms are relatively slow. | ||
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Estrogen and estrogen receptor proteins are known to have a wide variety of functions in multiple different tissue types. It is commonly known that estrogen acts as a morphogen, turning on genes that regulate sex differentiation and development. However, estrogen also plays an important role in other systems, such as the skeletal and cardiovascular systems. The specific genes that are turned on or off by estrogen in each cell type are influenced by what other compounds are in the cell. For example, the array of molecules in cardiovascular tissue is different from that of skeletal tissue, and thus the action of the estrogen-bound ER proteins are tissue-specific. | Estrogen and estrogen receptor proteins are known to have a wide variety of functions in multiple different tissue types. It is commonly known that estrogen acts as a morphogen, turning on genes that regulate sex differentiation and development. However, estrogen also plays an important role in other systems, such as the skeletal and cardiovascular systems. The specific genes that are turned on or off by estrogen in each cell type are influenced by what other compounds are in the cell. For example, the array of molecules in cardiovascular tissue is different from that of skeletal tissue, and thus the action of the estrogen-bound ER proteins are tissue-specific. | ||
The function of estrogen receptors has played a key role in the development of treatment strategies for many diseases, most notably for breast cancer. Drugs targeting ERs in cancerous breast tissue are designed as antagonists, suppressing ER activity in the cancerous tissue. Drugs targeting ER-α have been particularly effective at treating breast cancer.Other cancers that are strongly correlated with estrogen and ER activity are ovarian cancer, colon cancer, prostate cancer, and endometrial cancer. | The function of estrogen receptors has played a key role in the development of treatment strategies for many diseases, most notably for breast cancer. Drugs targeting ERs in cancerous breast tissue are designed as antagonists, suppressing ER activity in the cancerous tissue. Drugs targeting ER-α have been particularly effective at treating breast cancer. Other cancers that are strongly correlated with estrogen and ER activity are ovarian cancer, colon cancer, prostate cancer, and endometrial cancer. | ||
Drugs designed to act as agonists to ERs, increasing ER activity, have been used to treat osteoporosis. The symptoms of neurodegenerative diseases such as stroke, Parkinson's, and Alzheimer's, and cardiovascular diseases have been shown to be alleviated by estrogen and increased estrogen receptor activity. | Drugs designed to act as agonists to ERs, increasing ER activity, have been used to treat osteoporosis. The symptoms of neurodegenerative diseases such as stroke, Parkinson's, and Alzheimer's, and cardiovascular diseases have been shown to be alleviated by estrogen and increased estrogen receptor activity. | ||
Further research on the mechanism of estrogen receptor action is necessary to improve upon treatment methods. Understanding the recruitment of specific | Further research on the mechanism of estrogen receptor action is necessary to improve upon treatment methods. Understanding the recruitment of specific co-factors in different tissues, the importance of the ERα:ERβ ratio, and how the combination of these things can change a compound's ER antagonist and agonist action will perhaps enable us to treat diseases more specifically and with a smaller incidence of negative side effects. No effective clinical treatments have been developed to treat neurodegenerative diseases associated with estrogen activity. Research is needed to develop treatment for these and other diseases related to estrogen and estrogen receptor activity. | ||
== References == | == References == | ||
<references /> | <references /> | ||
