Why must ligands for intracellular receptors be lipid soluble?

• A. To remain in the extracellular space.
• B. To cross the plasma membrane.
• C. To be transported by ion channels.
• D. To degrade quickly in the cytosol.

Answer: (B)

Ligands for intracellular receptors must be lipid soluble because these receptors are inside the cell, so the ligand has to cross the plasma membrane to reach them. The cell membrane is a hydrophobic lipid bilayer, and lipid-soluble (nonpolar) molecules can dissolve in and diffuse through this interior, allowing them to access receptors in the cytoplasm or nucleus. Once inside, they bind the receptor and commonly influence gene expression or other slow cellular responses.

That’s why simply staying outside the cell, passing through ion channels, or degrading quickly in the cytosol don’t explain why lipid solubility is needed for intracellular receptor signaling.