Prednisolone - Mechanism of Action

Mechanism of Action

Prednisolone irreversibly binds with glucocorticoid receptors (GR) alpha and beta for which they have a high affinity. AlphaGR and BetaGR are found in virtually all tissues with variable numbers between 3000 and 10000 per cell, depending on the tissue involved. Prednisolone can activate and influence biochemical behaviour of most cells. The steroid/receptor complexes dimerise and interact with cellular DNA in the nucleus, binding to steroid-response elements and modifying gene transcription. They induce synthesis of some proteins, and inhibit synthesis of others.

Not all metabolic actions on genes are known. Most mediator proteins are enzymes, e.g., cAMP-dependent kinase

Anti-inflammatory and immunosuppressive actions:

• Inhibition of gene transcription for COX-2, cytokines, cell adhesion molecules, and inducible NO synthase
• Blockage of Vit D3-mediated induction of osteocalcin gene in osteoblasts
• Modification of collegenase gene transcription
• Increase synthesis annexin-1, important in negative feedback on hypothalamus and anterior pituitary gland

Regulation of gene suppression leads to systemic suppression of inflammation and immune response. This is of clinical usefulness but ultimately leads to gluconeogenesis, proteolysis and lipolysis. Gene transcription returns to normal after cessation, but sudden stoppage can cause Addison's disease. Osteoporosis is permanent.