Reduction in Cellular Protein. One of the principal effects of cortisol on the metabolic systems of the body is reduction of the protein stores in essentially all body cells except those of the liver. This is caused by both decreased protein synthesis and increased catabolism of protein already in the cells. Both these effects may result from decreased amino acid transport into extra-hepatic tissues, as discussed later; this probably is not the major cause, because cortisol also depresses the formation of RNA and subsequent protein synthesis in many extrahepatic tissues, especially in muscle and lymphoid tissue.
In the presence of great excesses of cortisol, the muscles can become so weak that the person cannot rise from the squatting position. And the immunity functions of the lymphoid tissue can be decreased to a small fraction of normal.
Cortisol Increases Liver and Plasma Proteins. Coinciden-tally with the reduced proteins elsewhere in the body, the liver proteins become enhanced. Furthermore, the plasma proteins (which are produced by the liver and then released into the blood) are also increased. These increases are exceptions to the protein depletion that occurs elsewhere in the body. It is believed that this difference results from a possible effect of cortisol to enhance amino acid transport into liver cells (but not into most other cells) and to enhance the liver enzymes required for protein synthesis.
Increased Blood Amino Acids, Diminished Transport of Amino Acids into Extrahepatic Cells, and Enhanced Transport into Hepatic Cells. Studies in isolated tissues have demonstrated that cortisol depresses amino acid transport into muscle cells and perhaps into other extrahepatic cells.
The decreased transport of amino acids into extra-hepatic cells decreases their intracellular amino acid concentrations and consequently decreases the synthesis of protein. Yet, catabolism of proteins in the cells continues to release amino acids from the already existing proteins, and these diffuse out of the cells to increase the plasma amino acid concentration. Therefore, cortisol mobilizes amino acids from the nonhep-atic tissues and in doing so diminishes the tissue stores of protein.
The increased plasma concentration of amino acids and enhanced transport of amino acids into the hepatic cells by cortisol could also account for enhanced utilization of amino acids by the liver to cause such effects as (1) increased rate of deamination of amino acids by the liver, (2) increased protein synthesis in the liver, (3) increased formation of plasma proteins by the liver, and (4) increased conversion of amino acids to glucose-that is, enhanced gluconeogenesis. Thus, it is possible that many of the effects of cortisol on the metabolic systems of the body result mainly from this ability of cortisol to mobilize amino acids from the peripheral tissues while at the same time increasing the liver enzymes required for the hepatic effects.
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