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The Mysterious Estrogen: Why Do Our Cells Need These Special Proteins?
Estrogen, as an important hormone, has a profound impact on the physiological functions of the human body. Estrogen receptors (ERs) are proteins found within cells that are responsible for receiving and regulating signals from this hormone. Not only do they play an important role in the development and function of the reproductive system, they also play key roles in bone health, the cardiovascular system, and many other physiological processes.
Estrogen receptors can be divided into two major categories: intracellular estrogen receptors (ERα and ERβ) and membrane estrogen receptors (mERs).
In humans, the genes for estrogen receptors are located on chromosomes six and fourteen. The functions of these receptors in cells are not limited to regulating gene expression, but are also involved in a series of rapid non-genomic signal transduction processes. The binding of estrogen triggers receptor translocation, ultimately affecting the expression of multiple genes and regulating cell function.
Structure and characteristics of estrogen receptor
Estrogen receptors usually appear in the form of dimers, divided into homodimers (ERαα or ERββ) and heterodimers (ERαβ). Each receptor is composed of five different domains, of which the A/B domain provides the necessary mechanism for the initiation of gene transcription, even in the absence of hormones. However, this hormone-free activation is relatively weak and appears to be more selective than the activation effect after hormone binding.
Significant sequence homology exists between estrogen receptors, allowing them to be co-expressed and interact in different cell types.
Signal transduction mechanism
The lipid solubility of estrogen allows it to easily cross cell membranes, which provides the possibility for the existence of estrogen receptors within cells and on the membrane. The binding of estrogen to the receptor causes the receptor to migrate from the cytoplasm to the nucleus, dimerize and bind to specific DNA sequences, thereby initiating the gene regulation process. The resulting DNA/receptor complex further recruits transcription-related proteins to promote the production of mRNA, ultimately affecting protein production and changes in cell function.
In addition to genomic pathways, estrogen can also rapidly activate cell surface receptors through non-genomic pathways, leading to the activation of multiple signaling pathways.
Clinical significance
Clinically, the expression of estrogen receptors is closely related to the formation of various cancers. Approximately 70% of breast cancers are classified as "ER-positive," and the presence of the receptor is typically confirmed by immunohistochemistry in such cancers. When estrogen binds to receptors, it promotes breast cell proliferation, thereby increasing the risk of tumor formation.
For the treatment of certain cancers, selective estrogen receptor modulators (SERMs) are used as treatment options to combat abnormalities in estrogen signaling.
The effects of menopause and aging
For postmenopausal women, the metabolic effects of estrogen are related to genetic polymorphisms in the estrogen receptor beta gene. Additionally, estrogen receptor alpha levels in female mice decline as they age, but studies have shown that long-term caloric restriction diets maintain their estrogen receptor alpha levels.
Obesity and estrogen receptor
Genetically engineered mice lacking functional aromatase exhibit characteristics of low estrogen levels and obesity. Estrogen plays an important role in regulating fat deposition, and estrogen-deficient female mice also develop significant obesity, suggesting a potential role for estrogen receptor alpha in regulating body weight.
Future research directions
Although our understanding of estrogen receptors has improved, there are still many unanswered questions that need to be explored. In particular, how the response of different tissues to the same ligand affects the efficacy and adverse reactions of the drug deserves further study. Currently, the world is working to find more effective treatments to combat estrogen-related diseases, including many cancers and other health problems.
In this research field full of challenges and opportunities, we can’t help but ask, how will future scientific research completely change our understanding of estrogen and its receptors?
