Macrocortin: a polypeptide causing the anti-phospholipase effect of glucocorticoids

Area of Science:

• Pharmacology
• Cell Biology
• Biochemistry

Background:

• Anti-inflammatory glucocorticoids inhibit prostaglandin (PG) biosynthesis.
• Steroid action involves receptor occupation and de novo protein/RNA synthesis.
• A previously identified 'second messenger' mediates steroid effects on PG generation.

Purpose of the Study:

• To characterize the 'second messenger' involved in steroid-mediated inhibition of PG biosynthesis.
• To identify and name the intracellular factor responsible for this effect.

Main Methods:

• Investigated the mechanism of glucocorticoid inhibition of prostaglandin synthesis.
• Utilized guinea pig perfused lungs and rat peritoneal leukocytes.
• Characterized the nature and regulation of the 'second messenger'.

Main Results:

• Identified an intracellular polypeptide, named 'macrocortin', as the mediator.
• Steroid administration stimulates the release and synthesis of macrocortin.
• Macrocortin from different tissues (guinea pig lungs, rat leukocytes) shows similarity.

Conclusions:

• Macrocortin is a key intracellular mediator of anti-inflammatory glucocorticoid action.
• The steroid-induced protein macrocortin inhibits prostaglandin biosynthesis.
• Macrocortin represents a novel target for anti-inflammatory therapies.