Intracellular receptors bind small hydrophobic signals inside the cytoplasm or nucleus and often regulate transcription directly, linking signal detection to a specific target-cell response.
Whether a signalling ligand crosses the phospholipid bilayer determines whether it binds a transmembrane receptor or an intracellular receptor.
| Feature | Transmembrane receptor | Intracellular receptor |
|---|---|---|
| Ligand | Usually hydrophilic; remains outside | Lipid-soluble, such as steroid hormones; crosses membrane |
| Location | Spans plasma membrane | Cytoplasm or nucleus |
| Amino-acid distribution | Hydrophobic residues face membrane lipids; hydrophilic regions face extracellular fluid/cytosol | Soluble receptor surface is mainly hydrophilic; ligand-binding pocket matches a hydrophobic ligand |
| Immediate effect | Starts an intracellular relay | Activated complex binds specific DNA sequences |
Oestradiol, progesterone and testosterone cross the membrane and bind intracellular receptors. The activated hormone–receptor complex binds specific DNA sequences and promotes transcription of target genes.
Receptor location follows ligand permeability and protein structure, not simply whether the signal is called a hormone. Protein hormones generally require surface receptors; steroid hormones use intracellular receptors.
A ligand only affects target cells with the matching receptor. Quorum sensing uses autoinducers and thresholds for group behaviour. Animal signals differ by source, distance, speed, target-cell response, and chemical class. Hydrophilic ligands use transmembrane receptors and relays; steroid and thyroid hormones use intracellular receptors that affect transcription. Named pathways then show the logic: acetylcholine opens sodium channels, GPCRs switch G proteins through GDP-GTP exchange, epinephrine uses cAMP and kinase cascades, insulin RTKs use dimerisation/autophosphorylation to move GLUT4 and promote glycogenesis, steroid hormones change gene expression, and feedback either amplifies or restores stability.