Hormone receptor
A hormone receptor is a
Hormonal therapy and hormone receptors play a very large part in breast cancer treatment (therapy is not limited to only breast cancer). By influencing the hormones, the cells' growth can be changed along with its function. These hormones can cause cancer to not survive in the human body.[4]
General ligand binding
Hormone receptor proteins bind to a hormone as a result of an accumulation of weak interactions. Because of the relatively large size of enzymes and receptors, the large amount of surface area provides the basis for these weak interactions to occur. This binding is actually highly specific because of the complementarity of these interactions between polar, non-polar, charged, neutral, hydrophilic, or hydrophobic residues. Upon binding, the receptor often undergoes a conformational change and may bind further, signaling ligands to activate a signaling pathway. Because of these highly specific and high affinity interactions between hormones and their receptors, very low concentrations of hormone can produce significant cellular response.[5] Receptors can have various different structures depending on the function of the hormone and the structure of its ligand. Therefore, hormone binding to its receptor is a complex process that can be mediated by cooperative binding, reversible and irreversible interactions, and multiple binding sites.[2]
Functions
Transmission of signal
The presence of hormone or multiple hormones enables a response in the receptor, which begins a cascade of signaling. The hormone receptor interacts with different molecules to induce a variety of changes, such as an increase or decrease of nutrient sources, growth, and other metabolic functions. These signaling pathways are complex mechanisms mediated by feedback loops where different signals activate and inhibit other signals. If a signaling pathway ends with the increase in production of a nutrient, that nutrient is then a signal back to the receptor that acts as a competitive inhibitor to prevent further production.[6] Signaling pathways regulate cells through activating or inactivating gene expression, transport of metabolites, and controlling enzymatic activity to manage growth and functions of metabolism.[7]
Intracellular receptors
Intracellular and nuclear receptors are a direct way for the cell to respond to internal changes and signals. Intracellular receptors are activated by hydrophobic ligands that pass through the cellular membrane. All nuclear receptors are very similar in structure, and are described with intrinsic transcriptional activity. Intrinsic transcriptional involves the three following domains:[8] transcription-activating,[9] DNA-binding,[10] and ligand-binding.[11] These domains and ligands are hydrophobic and are able to travel through the membrane.[12] The movement of macromolecules and ligand molecules into the cell enables a complex transport system of intracellular signal transfers through different cellular environments until response is enabled.[13] Nuclear receptors are a special class of intracellular receptor that specifically aid the needs of the cell to express certain genes. Nuclear receptors often bind directly to DNA by targeting specific DNA sequences in order to express or repress transcription of nearby genes.[1]
Cell surface receptors
The extracellular environment is able to induce changes within the cell. Hormones, or other extracellular signals, are able to induce changes within the cell by binding to cell surface receptors also known as transmembrane receptors.[5] This interaction allows the hormone receptor to produce second messengers within the cell to aid response. Second messengers may also be sent to interact with intracellular receptors in order to enter the complex signal transport system that eventually changes cellular function.[2]
G-protein-coupled membrane receptors (GPCR) are a major class of transmembrane receptors. The features of G proteins include GDP/GTP binding, GTP hydrolysis and guanosine nucleotide exchange.[14][15] When a ligand binds to a GPCR the receptor changes conformation, which makes the intracellular loops between the different membrane domains of the receptor interact with G proteins. This interaction causes the exchange of GDP for GTP, which triggers structural changes within the alpha subunit of the G protein.[16][15][14] The changes interrupts the interaction of the alpha subunit with the beta–gamma complex and which results in a single alpha subunit with GTP bound and a beta–gamma dimer. The GTP–alpha monomer interacts with a variety of cellular targets. The beta–gamma dimer also can stimulate enzymes within the cells for example, adenylate cyclase but it does not have as many targets as the GTP–alpha complex.[15]
Aiding gene expression
Hormone receptors can behave as transcription factors by interacting directly with DNA or by cross-talking with signaling pathways.[1] This process is mediated through co-regulators. In the absence of ligand, receptor molecules bind corepressors to repress gene expression, compacting chromatin through histone deacetylatase. When a ligand is present, nuclear receptors undergo a conformational change to recruit various coactivators. These molecules work to remodel chromatin. Hormone receptors have highly specific motifs that can interact with coregulator complexes.[17] This is the mechanism through which receptors can induce regulation of gene expression depending on both the extracellular environment and the immediate cellular composition. Steroid hormones and their regulation by receptors are the most potent molecule interactions in aiding gene expression.[1]
Problems with nuclear receptor binding as a result of shortages of ligand or receptors can have drastic effects on the cell. The dependency on the ligand is the most important part in being able to regulate gene expression, so the absence of ligand is drastic to this process. For example, estrogen deficiency is a cause of osteoporosis and the inability to undergo a proper signaling cascade prevents bone growth and strengthening. Deficiencies in nuclear receptor-mediated pathways play a key role in the development of disease, like osteoporosis.[18]
when a ligand binds to a nuclear receptor, the receptor undergoes a conformational change that causes it to become activated, which in turn affects how much gene expression is regulated.
Classification
Receptors for water-soluble hormones
Water-soluble hormones include
Water-soluble hormones come from amino acids and are located and stored in endocrine cells until actually needed.[20]
The main two types of
Receptors for lipid-soluble hormones
List of hormone receptors
For some of these classes, in any given species (such as, for example, humans), there is a single molecule encoded by a single gene; in other cases, there are several molecules in the class.
- Androgen receptors
- Calcitriol receptors
- Corticotropin-releasing hormone receptor 1
- Corticotropin releasing hormone receptor 2
- Estrogen receptors
- Follicle-stimulating hormone receptors
- Glucagon receptors
- Gonadotropin receptors
- Gonadotropin-releasing hormone receptors
- Growth hormone receptors
- Insulin receptor
- Luteinizing hormone
- Progesterone receptors
- Retinoid receptors
- Somatostatin receptors
- Thyroid hormone receptors
- Thyrotropin receptors
References
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- ^ "Understanding Hormone Receptors and What They Do". Breastcancer.org. Retrieved 2017-04-06.
- ^ a b Nelson 1, Cox 2, Lehninger 3. Principles of Biochemistry. New York: Worth. p. 81.
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- ^ "Mechanism of Action: Hormones with Intracellular Receptors". www.vivo.colostate.edu. Retrieved 2017-04-06.
- ^ "Molecular Biology". www.uh.edu. Retrieved 2017-04-06.
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- ^ "Ligand Binding Domain". www.ks.uiuc.edu. Retrieved 2017-04-06.
- ^ "Cell signalling". OpenLearn. Retrieved 2017-04-06.
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- ^ OCLC 1021173479.)
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- ^ Boundless (2016-10-23). "Mechanisms of Hormone Action". Boundless.
- ^ "e.hormone | Endocrine System : Types of Hormones". e.hormone.tulane.edu. Retrieved 2017-04-06.
- ^ "The Endocrine System". classes.midlandstech.edu. Retrieved 2017-04-06.
- ^ "Steroid Hormone Receptors and their Response Elements". Archived from the original on 2006-12-30. Retrieved 2006-05-01.
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