Learning Objective

Understand the mechanism of action, examples, and functional consequences of intracellular (nuclear) receptors, including their effects on gene expression and response timing.

Found in the cytoplasm or nucleus.

Ligands must be lipid-soluble to cross the cell membrane (e.g., steroids, thyroid hormones).

Mechanism of Action

1. Ligand enters the cell and binds to its intracellular receptor.
2. Binding causes release of regulatory proteins (e.g., heat-shock proteins).
3. The ligand–receptor complex activates, often dimerizes, and translocates to the nucleus.
4. It binds specific hormone response elements (HREs) on DNA.
5. This leads to increased or decreased gene transcription, ultimately changing protein synthesis.

Examples of Intracellular Receptors

• Glucocorticoids → induce proteins that suppress inflammatory mediators
• Thyroid hormones (T3/T4)
• Gonadal steroids (estrogen, progesterone, testosterone)
• Vitamin D (calcitriol receptor)

Response Characteristics

• Slow onset (hours to days)
  – Because changes require transcription and translation
• Long duration
  – Effects persist as new proteins remain active for long periods

Activity