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== Introduction == | == Introduction == | ||
Estrogen receptors (ER) belong to the super family of nuclear receptor proteins (NRP). Nuclear receptor proteins are a diverse group of proteins located in the nucleus. These proteins bind to specific ligands and undergo conformational changes, whereby they can then act as transcription factors to up-regulate or down-regulate certain genes. Nuclear hormone receptors (NHR) are a subgroup of NRPs that have hormone ligands. Estrogen receptors are nuclear hormone receptors whose ligand is estrogen.<ref>Olefsky, J. M. (2001). Nuclear receptor minireview series. The Journal of Biological Chemistry, 276, 36863-36864. [http://www.jbc.org/content/276/40/36863 doi:10.1074/jbc.R100047200]</ref> NRPs are found only in animals.<ref>ESCRIVA, H., LANGLOIS, M.-, MENDONÇA, R., MENDONÇA, L., PIERCE, R., & LAUDET, V. (2006). Evolution and diversification of the nuclear receptor superfamily. The Annals of the New York Academy of Sciences, 839(1), 143-146. Retrieved from [http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1998.tb10747.x/pdf]</ref> | The activity of estrogen and estrogen receptors has been linked to several cancers, including breast cancer, ovarian cancer, and colon cancer, as well as skeletal and cardiovascular diseases. The use of antagonist or agonist compounds with regards to the ligand-binding effect on the estrogen receptor has been used as a treatment method for breast cancer and osteoporosis. <ref>PMID:16511588</ref> | ||
Estrogen receptors (ER) belong to the super family of nuclear receptor proteins (NRP). Nuclear receptor proteins are a diverse group of proteins located in the nucleus. These proteins bind to specific ligands and undergo conformational changes, whereby they can then act as transcription factors to up-regulate or down-regulate certain genes. Nuclear hormone receptors (NHR) are a subgroup of NRPs that have hormone ligands. Estrogen receptors are nuclear hormone receptors whose ligand is estrogen.<ref>Olefsky, J. M. (2001). Nuclear receptor minireview series. The Journal of Biological Chemistry, 276, 36863-36864. [http://www.jbc.org/content/276/40/36863 doi:10.1074/jbc.R100047200]</ref> NRPs are found only in animals. Mouse and rat models are commonly used to research the function of ER due to the similarity of ER function. <ref>ESCRIVA, H., LANGLOIS, M.-, MENDONÇA, R., MENDONÇA, L., PIERCE, R., & LAUDET, V. (2006). Evolution and diversification of the nuclear receptor superfamily. The Annals of the New York Academy of Sciences, 839(1), 143-146. Retrieved from [http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1998.tb10747.x/pdf]</ref> | |||
There are two types of estrogen receptors: estrogen receptor-α and estrogen receptor-β. There has been much research done on both ER-α and ER-β, and it is still unclear exactly how each functions. However, like all NRPs, the ER proteins have a highly conserved DNA-binding domain, a specific ligand-binding domain, and a highly variable N-terminus region. In ER proteins, the ligand-binding domain is located near the C-terminal region of the protein. Once bound, the mechanism of transcriptional regulation is dependent upon what co-factors and other signalling molecules are present in the cell.<ref>PMID:11581496</ref> | There are two types of estrogen receptors: estrogen receptor-α and estrogen receptor-β. There has been much research done on both ER-α and ER-β, and it is still unclear exactly how each functions. However, like all NRPs, the ER proteins have a highly conserved DNA-binding domain, a specific ligand-binding domain, and a highly variable N-terminus region. In ER proteins, the ligand-binding domain is located near the C-terminal region of the protein. Once bound, the mechanism of transcriptional regulation is dependent upon what co-factors and other signalling molecules are present in the cell.<ref>PMID:11581496</ref> | ||
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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. | 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. | |||
Further research on the mechanism of estrogen receptor action is necessary to improve upon treatment methods. Understanding the recruitment of specific cofactors 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 use to treat diseases more specifically and with a smaller incidence of negative side effects. | Further research on the mechanism of estrogen receptor action is necessary to improve upon treatment methods. Understanding the recruitment of specific cofactors 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 use 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 /> | ||
