• Metabolic Effects:
  • Glucocorticoids: stimulate and are required for:
    • gluconeogenesis (fasted state, diabetes);
    • increasing hepatic and renal amino acid uptake
    • increase gluconeogenic enzyme activity
  • Hepatic effects:
    • Simulation of glycogen synthase
    • Increase glucose production from protein-- stimulating insulin release
  • Adipocytes:
    • inhibit glucose uptake promoting increased lipolysis
    • counteracted by enhanced insulin secretion which stimulates lipogenesis
    • net effect: fat deposition

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  • Glucocorticoid effects most prominent in the fasting state, through:
    • stimulation:gluconeogenesis
    • stimulation: amino acid release from muscle (catabolism)
    • inhibition: peripheral glucose uptake
    • stimulation: lipolysis

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• Catabolic Effects:
  • promotion of catabolism:
    • lymphoid tissue
    • connective tissue
    • muscle
    • fat
    • skin
  • High (supraphysiologic) glucocorticoid levels cause:
    • decreased muscle mass, weakness
  •  reduced growth in children (not prevented by growth hormone)
  • Catabolic effects on bone:
    •  osteoporosis in Cushing's syndrome
    •  major limitation in long-term use

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• Anti-inflammatory/Immunosuppressive Effects:
  • Reduce inflammation --
    • Leukocyte-mediated; reduced leukocyte infiltration
    • glucocorticoid inhibition of interactions involving cell adhesion molecules (especially on endothelial cells)
    • Following glucocorticoid administration:
      • neutrophils, but
      • lymphocytes (T and B cells, monocytes, eosinophils, basophils-- movement from vasculature to lymphoid tissue)
    • Glucocorticoids inhibit:
      • leukocyte and tissue macrophage function
      • reduced antigenic and mitogenic responsiveness
      • Macrophage effects:
        • interferon-gamma, interleukin 1, pyrogen, collagenase, elastase, tumor necrosis factor, plasminogen activator
      • Lymphocyte effects:
        • interleukin 2
    • Reduction of prostaglandin and leukotriene synthesis (resulting from phospholipase A₂ activation)
    • Reduction of cyclooxygenase in inflammatory cells (reducing prostaglandin synthesis)
      • of the two isoforms of cyclooxygenase (COX1 and COX-II), glucocorticoids inhibit COX-II gene expression.
    • Glucocorticoids decrease capillary permeability by:
      1. reducing kinin activity
      2. reducing bacterial endotoxin activity
      3. reducing basophils histamine release

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• Other Effects:
  • adrenal-insufficiency: EEG changes (slowing of alpha rhythms)
  • increased levels: behavioral changes;
  • pituitary release of ACTH and beta-lipotropin
  • TSH and FSH secretion
  • excess acid/pepsin production (large doses)
  • fat absorption
  • in addition: effective vitamin D on calcium absorption
  • platelet production, erythrocyte production
  • without adequate cortisol: renal function -- impaired
  • Glucocorticoids important infield of element (structure/functional changes in the lung)

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