6.2
Internal Receptors
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cro…
Internal receptors are soluble proteins found in either the cytoplasm or the nucleus. They bind signaling molecules called ligands inside the cell and trigger cellular responses, such as changes in gene expression.
Typically, ligands that bind to internal receptors are hydrophobic, nonpolar molecules that can diffuse through the plasma membrane without needing a membrane receptor. Some signaling molecules can also be synthesized inside the target cell.
Once a ligand binds, the receptor changes shape and interacts with other regulatory elements in the cell.
For example, the hormone testosterone, or its converted form dihydrotestosterone, also called DHT, binds to androgen receptors located in the cytoplasm.
After binding, the receptor-ligand complex changes structure and exposes its DNA-binding region. This change also allows the receptors to form dimers and move into the nucleus.
Inside the nucleus, the activated receptor binds to specific DNA sequences called hormone-response elements. In androgen signaling, these sequences are called androgen-response elements.
By binding to these DNA sequences, the receptor recruits other cellular machinery that helps regulate gene activity by increasing or decreasing the expression of specific target genes.
These changes in gene expression lead to androgen-related effects in target tissues, such as muscles, the prostate, and hair follicles.
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Q1: What types of signaling molecules can bind to internal receptors?
Internal receptors bind hydrophobic, non-polar signaling molecules that can diffuse through the plasma membrane, such as steroid hormones like testosterone and estrogen. Some ligands are synthesized intracellularly, like nitric oxide gas. These molecules differ from hydrophilic signals that cannot cross the membrane and require membrane-bound receptors instead.
Q2: How does testosterone activate gene expression through internal receptors?
When testosterone or its converted form DHT binds to an androgen receptor in the cytoplasm, the ligand-receptor complex undergoes conformational changes, moves to the nucleus, and dimerizes. The activated complex then binds to DNA-binding sites called androgen-response elements, which modulate gene activity by promoting or blocking mRNA synthesis to produce androgen-specific cellular effects.
Q3: Why must cytoplasmic internal receptors cross the nuclear membrane?
Cytoplasmic internal receptors must cross the nuclear membrane because their target DNA-binding sites, called response elements, are located in the nucleus. Once the ligand-receptor complex forms in the cytoplasm, it translocates across the nuclear membrane to access these specific DNA sequences and regulate transcription of target genes.
Q4: What happens when estrogen binds to its intracellular receptor?
Estrogen diffuses across the plasma membrane and binds to its cytoplasmic receptor, triggering dimerization of receptor molecules. The ligand-receptor complex then transports to the nucleus and binds to Estrogen-Response Elements (EREs) on DNA. Depending on co-activators and other transcription factors present, this binding increases or decreases transcription of target genes.
Q5: How do thyroid hormone receptors differ in their cellular location?
Unlike steroid hormone receptors that reside in the cytoplasm, some thyroid hormone receptors are located directly in the nucleus. These nuclear-resident receptors require ligands to cross both the plasma membrane and nuclear membrane to reach them. Once activated, they bind to DNA and regulate transcription similarly to cytoplasmic internal receptors.
Q6: What conformational changes occur when a ligand binds to an internal receptor?
Ligand binding induces a conformational change in the internal receptor that enables it to bind other cellular molecules. This structural rearrangement allows the receptor to expose its DNA-binding domain, facilitating dimerization and nuclear translocation. The activated receptor can then recognize and bind specific DNA sequences to regulate gene expression.
Q7: How do response elements control gene activity after receptor binding?
Response elements are specific DNA sequences recognized by activated internal receptor complexes. When receptors bind to these sites, they either promote or block mRNA synthesis of target genes depending on the presence of co-activators and other transcription factors. This mechanism allows cells to produce hormone-specific responses through selective gene regulation.