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Glucocorticoid modulation of cardiac mass and protein
1Department of Medicine, University of Chicago, IL 60637.
Abstract:
We have examined glucocorticoid actions in the heart on the basis of their ability to 1) produce changes in ventricular mass, 2) influence total protein synthesis, and 3) alter myosin, a glucocorticoid-inducible protein. Cardiac hypertrophy of 6-20% has been demonstrated following treatment with various natural or synthetic steroids. The enlargement can occur rapidly within 2 d, yet recent evidence suggests that the increased mass is lost with prolonged treatment. Total protein synthesis rates have not been consistently observed to increase during the growth phase and are reduced to 50-60% of control rates by 7 d of hormone injections. Myosin heavy chain synthesis also is not elevated during the growth phase and is also reduced by 1 wk of treatment. Ventricular relative isomyosin content (V1, V2, V3), as determined by pyrophosphate gel electrophoresis, is shifted from V1 to V3 by approximately 10% after 11 d of steroid treatment. These results demonstrate that the glucocorticoid induction of increased ventricular mass is temporary under certain conditions. The down-regulation of the myosin heavy chains may prove as a potentially important protein for understanding the regulation of cardiac catabolism caused by glucocorticoids.
Insights
Glucocorticoids can temporarily increase heart size, but this effect diminishes with prolonged exposure. Myosin heavy chain regulation is key to understanding steroid-induced cardiac catabolism.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Glucocorticoids are known to affect cardiac function.
- Cardiac hypertrophy is a potential outcome of steroid treatment.
Purpose of the Study:
- To investigate glucocorticoid effects on ventricular mass, protein synthesis, and myosin.
- To understand the regulation of cardiac catabolism by glucocorticoids.
Main Methods:
- Steroid treatment in animal models.
- Measurement of ventricular mass.
- Assessment of total protein and myosin heavy chain synthesis.
- Analysis of isomyosin content using pyrophosphate gel electrophoresis.
Main Results:
- Glucocorticoids induced a temporary 6-20% increase in ventricular mass.
- Total protein and myosin heavy chain synthesis rates decreased by 7 days of treatment.
- Isomyosin profile shifted from V1 to V3 after 11 days of steroid administration.
Conclusions:
- Glucocorticoid-induced cardiac hypertrophy is transient.
- Down-regulation of myosin heavy chains is crucial for understanding glucocorticoid-mediated cardiac catabolism.