Гормональные рецепторы: структура, функции и роль в терапии

Group of proteins
A hormone receptor is a receptor molecule that binds to a specific hormone. Hormone receptors are a wide family of proteins made up of receptors for thyroid and steroid hormones, retinoids and Vitamin D, and a variety of other receptors for various ligands, such as fatty acids and prostaglandins. Hormone receptors are of mainly two classes. Receptors for peptide hormones tend to be cell surface receptors built into the plasma membrane of cells and are thus referred to as trans membrane receptors. An example of this is Actrapid. Receptors for steroid hormones are usually found within the protoplasm and are referred to as intracellular or nuclear receptors, such as testosterone. Upon hormone binding, the receptor can initiate multiple signaling pathways, which ultimately leads to changes in the behavior of the target cells. 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.

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. 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. Signaling pathways regulate cells through activating or inactivating gene expression, transport of metabolites, and controlling enzymatic activity to manage growth and functions of metabolism.

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: transcription activating, DNA binding, and ligand binding. These domains and ligands are hydrophobic and are able to travel through the membrane. 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. 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. 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. 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. 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.

Water soluble hormones include glycoproteins, catecholamines, and peptide hormones composed of polypeptides, e. g. thyroid stimulating hormone, follicle stimulating hormone, luteinizing hormone and insulin. These molecules are not lipid soluble and therefore cannot diffuse through cell membranes. Consequently, receptors for peptide hormones are located on the plasma membrane because they have bound to a receptor protein located on the plasma membrane. Water soluble hormones come from amino acids and are located and stored in endocrine cells until actually needed. The main two types of transmembrane receptor hormone receptor are the G protein coupled receptors and the enzyme linked receptors. These receptors generally function via intracellular second messengers, including cyclic AMP (cAMP), cyclic GMP (cGMP), inositol 1,4,5 trisphosphate (IP3) and the calcium (Ca2+) calmodulin system.

Steroid hormone receptors and related receptors are generally soluble proteins that function through gene activation. Lipid soluble hormones target specific sequences of DNA by diffusing into the cell. When they have diffused into the cell, they bind to receptors (intracellular), and migrate into the nucleus. Their response elements are DNA sequences (promoters) that are bound by the complex of the steroid bound to its receptor. The receptors themselves are zinc finger proteins. These receptors include those for glucocorticoids (glucocorticoid receptors), estrogens (estrogen receptors), androgens (androgen receptors), thyroid hormone (T3) (thyroid hormone receptors), calcitriol (the active form of vitamin D) (calcitriol receptors), and the retinoids (vitamin A) (retinoid receptors). Receptor protein interactions induce the uptake and destruction of their respective hormones in order to regulate their concentration in the body. This is especially important for steroid hormones because many body systems are entirely steroid dependent.