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Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range.
Open accessAbstract
Prolonged exposure to glucocorticoids in pharmacologic amounts results in muscle wasting, but whether changes in plasma cortisol within the physiologic range affect amino acid and protein metabolism in man has not been determined. To determine whether a physiologic increase in plasma cortisol increases proteolysis and the de novo synthesis of alanine, seven normal subjects were studied on two occasions during an 8-h infusion of either hydrocortisone sodium succinate (2 micrograms/kg X min) or saline. The rate of appearance (Ra) of leucine and alanine were estimated using [2H3]leucine and [2H3]alanine. In addition, the Ra of leucine nitrogen and the rate of transfer of leucine nitrogen to alanine were estimated using [15N]leucine. Plasma cortisol increased (10 +/- 1 to 42 +/- 4 micrograms/dl) during cortisol infusion and decreased (14 +/- 2 to 10 +/- 2 micrograms/dl) during saline infusion. No change was observed in plasma insulin, C-peptide, or glucagon during either saline or cortisol infusion. Plasma leucine concentration increased more (P less than 0.05) during cortisol infusion (120 +/- 1 to 203 +/- 21 microM) than saline (118 +/- 8 to 154 +/- 4 microM) as a result of a greater (P less than 0.01) increase in its Ra during cortisol infusion (1.47 +/- 0.08 to 1.81 +/- 0.08 mumol/kg X min for cortisol vs. 1.50 +/- 0.08 to 1.57 +/- 0.09 mumol/kg X min). Leucine nitrogen Ra increased (P less than 0.01) from 2.35 +/- 0.12 to 3.46 +/- 0.24 mumol/kg X min, but less so (P less than 0.05) during saline infusion (2.43 +/- 0.17 to 2.84 +/- 0.15 mumol/kg X min, P less than 0.01). Alanine Ra increased (P less than 0.05) during cortisol infusion but remained constant during saline infusion. During cortisol, but not during saline infusion, the rate and percentage of leucine nitrogen going to alanine increased (P less than 0.05). Thus, an increase in plasma cortisol within the physiologic range increases proteolysis and the de novo synthesis of alanine, a potential gluconeogenic substrate. Therefore, physiologic changes in plasma cortisol play a role in the regulation of whole body protein and amino acid metabolism in man.
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“Because GCs are known to promote the catabolism of proteins, including serum albumin (, ), there is a risk that GA levels will be influenced by GC excess.”
From Glucose Metabolism Abnormalities in Cushing Syndrome: From Molecular Basis to Clinical Management (2017) · cites this paper as [242]
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Qulali, M., & Crabb, D. W. (1992) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1992.tb01394.x · Cited by 14
HPA hyperactivity with increased plasma cortisol affects dexamethasone metabolism and DST outcome
Stokes, P. E., Sikes, C. R., Lasley, B., & Stoll, P. (2002) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(02)00059-6 · Cited by 14
“It is more than probable that the degradation of cortisol and dexamethasone share common pathways (Simmons et al., 1984).”
BackgroundLeucine metabolism in patients with Cushing's syndrome before and after successful treatment
Bowes, S. B., Benn, J. J., Scobie, I. N., Umpleby, A. M., Lowy, C., & Sönksen, P. H. (1993) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1993.tb02414.x · Cited by 14
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Hormonal response to lipid and carbohydrate meals during the acute postprandial period
Alleman, R. J., & Bloomer, R. J. (2011) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-8-19 · Cited by 13
“For cortisol, a further lowering during the postprandial period may be viewed as positive, as lower cortisol may be associated with decreased proteolysis [35]–also important when considering anabolism.”
BackgroundEffects of chronic hypercortisolemia on carbohydrate metabolism during insulin deficiency
Goldstein, R. E., Cherrington, A. D., Reed, G. W., Lacy, D. B., Wasserman, D. H., & Abumrad, N. N. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.4.e618 · Cited by 13
Harrigan, M. E., Filous, A. R., Vadala, C. P., Webb, A., Pietrzak, M., Sahenk, Z., Prüß, H., Reiser, P. J., Popovich, P. G., Arnold, W. D., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adh2156 · Cited by 12
“…to even modest circulating glucocorticoid fluctuations ( 40 , 41 ), with severe/continued elevations drawing heavily on skeletal muscle energy stores ( 42 , 43 ), and suggests that these steroid hormones can be targeted to attenuate systemic muscle wasting even at lower injury lesion levels.”
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Cortisone effects on growth, food efficiency, and in vitro growth hormone release
Krieg, R. J., Niimi, K., Chan, J. C. M., Santos, F., Hanna, J. D., & Poletti, L. F. (1991) · Kidney International · doi:10.1038/ki.1991.144 · Cited by 12
Nuttall, F. Q., & Gannon, M. C. (2012) · Nutrition & Metabolism · doi:10.1186/1743-7075-9-43 · Cited by 12
“However, this could be offset by elevated cortisol and glucagon concentrations [10-13].”
BackgroundHypercortisolemia decreases dexamethasone half-life in rabbit
Stokes, P. E., Stoll, P., Schluger, J. H., & Lasley, B. (2002) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(02)00012-2 · Cited by 12
“Even increased plasma cortisol levels within the physiological range increases proteolysis (Simmons et al., 1984).”
BackgroundInfluentialHellstern, G., Reijngoud, D., Stellaard, F., & Okken, A. (1996) · Pediatric Research · doi:10.1203/00006450-199603000-00008 · Cited by 11
Amino Acid Kinetics During the Anhepatic Phase of Liver Transplantation
Battezzati, A., Caumo, A., Fattorini, A., Sereni, L. P., Coppa, J. C., Romito, R., Ammatuna, M., Regalia, E., Mazzaferro, V., & Luzi, L. (2002) · Diabetes · doi:10.2337/diabetes.51.6.1690 · Cited by 11
“Cortisol also increases the substrate availability (29), but it requires several hours to increase proteolysis and the glutamine and alanine de novo synthesis (30,31).”
BackgroundExercise and Protein Metabolism
Evans, W. J. (2015) · World review of nutrition and dietetics · doi:10.1159/000422347 · Cited by 10
Effect of Dietary Tryptophan Supplementation on Blood Biochemical Parameters in Layer Chicken
Preedaa, M. G., Selvaraj, P., Visha, P., Purushothaman, M. R., & Murali, N. (2017) · International Journal of Current Microbiology and Applied Sciences · doi:10.20546/ijcmas.2017.607.173 · Cited by 10
“Further, tryptophan inhibits the expression of cathepsin B and 20S protease and plasma cortisol secretion thus inhibiting protein degradation (Simmons et al., 1984).”
BackgroundMangine, G. T., VanDusseldorp, T. A., Hester, G. M., Julian, J. M., & Feito, Y. (2020) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-020-00359-4 · Cited by 10
Glycerol metabolism in humans: validation of2H- and13C-labelled tracers
Matthews, D. E., Pesola, G. R., & Kvetan, V. (1991) · Acta Diabetologica · doi:10.1007/bf00579723 · Cited by 10
“Later studies used a 3H or 2H restricted to the tail of the alanine [3-6] to avoid the problem of loss of the 2nd position hydrogen by transamination.”
MethodMuscle protein synthesis in steroid‐induced proximal myopathy: A case report
Pacy, P. J., & Halliday, D. (1989) · Muscle & Nerve · doi:10.1002/mus.880120507 · Cited by 10
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“One of the most important effects of cortisol is muscle proteolysis, resulting in the release of amino acids to the bloodstream, activation of liver gluconeogenesis and increased liver glucose release (Simmons et al., 1984).”
BackgroundHormones as Performance- Enhancing Drugs
Myhal, M., & Lamb, D. R. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-016-2_24 · Cited by 9
Impaired utilization of exogenous amino acids after surgery for subarachnoid haemorrhage
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Plasma Amino Acid Profiles in Collagen Disease Patients with Interstitial Lung Disease
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Effect of glucagon immunoneutralization on the increase in urea synthesis after hysterectomy in rats
Heindorff, H., Holst, J. J., Almdal, T., & Vilstrup, H. (1993) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1993.tb00756.x · Cited by 9
Tessitore, L., Bonelli, G., Isidoro, C., Kazakova, O. V., & Baccino, F. M. (1986) · Toxicologic Pathology · doi:10.1177/019262338601400411 · Cited by 9
Hormone and Cytokine Regulation of Injury Metabolism
Lowry, S. F. (1993) · Springer eBooks · doi:10.1007/978-3-642-84904-6_1 · Cited by 9
Role of Stress and Hormones of the Hypothalamic-Pituitary-Adrenal (HPA) Axis in Aging
Gupta, A. (2019) · Springer eBooks · doi:10.1007/978-981-13-3585-3_12 · Cited by 8
Malmlöf, K., Johansen, P. B., Haahr, P.-M., Wilken, M., & Oxlund, H. (1999) · Growth Hormone & IGF Research · doi:10.1054/ghir.1999.0128 · Cited by 8
Metadata
- Authors
- Simmons, P. S., Miles, J. M., Gerich, J. E., & Haymond, M. W.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Haymond, M W
- Venue
- Journal of Clinical Investigation
- Published
- 1984-02-01
- Volume
- 73
- Issue
- 2
- Pages
- 412-420
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC425032
- OpenAlex
- W2075956591
- Cited by
- 286
- References
- 41
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 13 · 2020: 15 · 2019: 6 · 2018: 6 · 2017: 14 · 2016: 2 · 2015: 6 · 2014: 10 · 2013: 11 · 2012: 3
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wasie Foundation
- Mayo Foundation for Medical Education and Research
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- plasma cortisol, proteolysis, leucine kinetics, alanine synthesis, amino acid metabolism, protein metabolism, muscle atrophy, insulin, glucagon, C-peptide, nitrogen balance, muscle protein turnover, nitrogen retention, nitrogen excretion, nitrogen intake
- MeSH terms
- Adult, Alanine, Amino Acids, Blood Glucose, Humans, Hydrocortisone, Kinetics, Leucine, Nitrogen, Peptide Hydrolases
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