21.4
Types of Receptors: Internal Receptors
Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hyd…
Internal receptors are soluble proteins that bind signaling molecules inside cells, either in the cytoplasm or nucleus, to trigger responses, such as changes in gene expression.
Typically, the ligands that bind to internal receptors are hydrophobic, non-polar molecules that diffuse through the plasma membrane of the targeted cells or are compounds that may be synthesized intracellularly.
For example, the hormone testosterone or its enzymatically processed form dihydrotestosterone, or DHT, binds to an androgen receptor in the cytoplasm.
The receptor-ligand complexes move into the nucleus and dimerize. The DNA-binding site of the receptor recognizes and binds to specific nucleotide sequences called hormone or androgen-response elements.
The binding modulates the activity of specific genes, either promoting or blocking the synthesis of mRNAs that mediate androgen-specific effects in cells.
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Q1: What are internal receptors and how do they differ from cell surface receptors?
Internal receptors are soluble proteins located in the cytoplasm or nucleus that bind hydrophobic signaling molecules inside cells. Unlike types of receptors cell surface receptors, which bind hydrophilic ligands outside the cell, internal receptors allow small, non-polar molecules to diffuse through the plasma membrane and trigger intracellular responses such as changes in gene expression.
Q2: What types of signaling molecules can bind to internal receptors?
Internal receptors bind hydrophobic, non-polar signaling molecules that can cross the plasma membrane. Examples include steroid hormones like testosterone and estrogen, their enzymatically processed forms such as dihydrotestosterone (DHT), and nitric oxide gas. These molecules either diffuse through the membrane or are synthesized within the cell.
Q3: How does the androgen receptor pathway work after testosterone binding?
When testosterone or DHT binds to the androgen receptor in the cytoplasm, the receptor-ligand complex undergoes a conformational change and moves into the nucleus where it dimerizes. The activated receptor recognizes and binds to specific DNA sequences called androgen-response elements, modulating gene activity to promote or block synthesis of mRNAs that mediate androgen-specific cellular effects.
Q4: Why must cytoplasmic internal receptors cross the nuclear membrane?
Internal receptors located in the cytoplasm must cross the nuclear membrane because their target DNA-binding sites are located within the nucleus. After ligand binding and dimerization, the activated receptor-ligand complex translocates into the nucleus to access hormone or androgen-response elements and regulate transcription of target genes.
Q5: What happens when estrogen binds to its intracellular receptor?
Estrogen diffuses across the plasma membrane and binds to its intracellular receptor, causing receptor dimerization. The ligand-receptor complex then enters the nucleus and binds to Estrogen-Response Elements (EREs) on DNA. Depending on associated transcription factors and co-activators, this binding increases or decreases transcription of target genes.
Q6: How do internal receptors regulate gene expression?
Once activated by ligand binding, internal receptors function like transcription factors by binding to specific DNA sequences called response elements. This binding modulates the activity of target genes, either promoting or blocking mRNA synthesis. The outcome depends on the receptor type, DNA sequence, and presence of other transcription factors and co-activators.
Q7: Where are thyroid hormone receptors typically located in the cell?
Thyroid hormone receptors usually reside in the nucleus, unlike cytoplasmic internal receptors. Because these receptors are already nuclear, their ligands must cross both the plasma membrane and nuclear membrane to reach and activate them. This nuclear localization distinguishes thyroid hormone signaling from steroid hormone pathways that begin in the cytoplasm.