Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range

Area of Science:

• Endocrinology
• Human Metabolism
• Biochemistry

Background:

• Pharmacologic glucocorticoid doses induce muscle wasting.
• The impact of physiological cortisol levels on human amino acid and protein metabolism remains unclear.

Purpose of the Study:

• To investigate whether physiological elevations in plasma cortisol enhance proteolysis and de novo alanine synthesis in humans.

Main Methods:

• Seven healthy subjects received infusions of hydrocortisone or saline over 8 hours.
• Stable isotope tracers ([2H3]leucine, [2H3]alanine, [15N]leucine) were used to measure amino acid appearance rates and nitrogen transfer.
• Plasma cortisol, insulin, C-peptide, and glucagon levels were monitored.

Main Results:

• Cortisol infusion significantly increased plasma cortisol, leucine concentration, leucine appearance rate (Ra), and leucine nitrogen Ra.
• Alanine Ra and the transfer of leucine nitrogen to alanine also increased significantly during cortisol infusion.
• No significant changes in insulin, C-peptide, or glucagon were observed.

Conclusions:

• Physiological increases in plasma cortisol stimulate whole-body proteolysis.
• Cortisol promotes the de novo synthesis of alanine, a potential gluconeogenic substrate.
• Physiological cortisol variations play a role in regulating human protein and amino acid metabolism.