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Cortisol (Hydrocortisone) Print E-mail

Dr. Kennedy Cortisol is a corticosteroid hormone produced in the cortex (outermost layer) of the adrenal gland, in two layers name the Zona fasciculata and Zona reticularis. It is a vital hormone often referred to as the "stress hormone" because it is involved in the response to stress. Cortisol increases blood pressure and blood sugar levels and is an immunosuppressive as well. The synthetic form of cortisol is referred to as hydrocortisone, and is used as an antagonist in the treatment of allergies and inflammation as well as a treatment in cortisol production deficiencie disorders such as hypoadrenalism and Addison's disease.

The storage form of cortisol is cortisone. Cortisol has much greater glucocorticoid activity than cortisone and thus cortisone is considered a relatively inactive metabolite of cortisol. 11-beta-steroid dehydrogenase can catalyze the reverse reaction and thus cortisone is also the inactive precursor (storage) molecule of the active hormone cortisol. Cortisone is activated through hydrogenation of the 11-keto-group by 11-beta-steroid dehydrogenase. Cortisol is thus sometimes referred to as hydrocortisone.

The amount of cortisol present in the blood varies through the 24 hour cycle, with the highest levels present in the early morning, and the lowest levels present around midnight, 3-5 hours after the onset of sleep. The light/dark cycle has a strong role in this regulation and is transmitted from the retina to the paired suprachiasmatic nuclei in the hypothalamus. The pattern is not present at birth but begins from two weeks to 9 months. There is significant individual variation, although a given person tends to have consistent rhythms. Conditions which change cortisol levels are:

  • abnormal ACTH levels
  • clinical depression
  • extremes of ambient temperature
  • psychological stress
  • hypoglycemia
  • trauma
  • surgery
  • pain
  • physical exertion
  • illness
  • fever
  • fear

Cortisol has widespread actions which help restore homeostasis after stress. The consequence of chronic stress is prolonged cortisol secretion. It is believed that its primary function is to inversely mobilize the immune system to fight potassium-depleting diarrhea diseases. Its known actions all seem support this idea.


  • increases glycolysis (break down glycogen to glucose in the liver and in skeletal muscle)
  • increases gluconeogenesis (the manufacture of glucose in the liver)

These actions add up to the fact that prolonged cortisol secretion causes hyperglycemia (elevated blood glucose).


  • promotes breakdown of lipids (lipolysis), and proteins
  • mobilizes amino acids
  • stimulates gastric acid secretion

The action of cortisol are still under investigation. Here are some miscellaneous facts about this most complex of hormones:

  • causes serum glucose to rise, probably caused by stimulation of amino acid degradation, especially that derived from collagen in the skin. As stated above, cortisol raises the free amino acids in the serum. It does this by inhibiting collagen formation, decreasing amino acid uptake by muscle, and inhibiting protein synthesis.
  • stimulates gastric acid secretion this would accelerate loss of potassium into the stomach during diarrhea as well as acid loss.
  • causes alkalosis of the serum, while in a deficiency pH does not change
  • acts as a water diuretic hormone causing water loss both from the gut and the kidneys
  • can weaken the activity of the immune system by preventing proliferation of T-cells
  • lowers bone formation thus favoring development of osteoporosis
  • cooperates with epinephrine (adrenaline) to create memories of short-term emotional events; this is the proposed mechanism for storage of "flash bulb" memories, and may originate as a means to remember what to avoid in the future. However, long-term exposure to cortisol results in damage to cells in the hippocampus and this damage impairs learning.
  • creates euphoria
  • increases blood pressure by increasing the sensitivity of the vasculature to epinephrine and norepinephrine; in the absence of cortisol, widespread vasodilation occurs
  • inhibits the secretion of corticotropin-releasing hormone (CRH), resulting in feedback inhibition of ACTH secretion. This normal feedback system may break down when exposed to chronic stress
  • increases the effectiveness of catecholamine
  • allows for the kidneys to produce hypotonic urine
  • has anti-inflammatory effects by reducing histamine secretion
  • stimulates hepatic detoxification.
  • 96% bound to proteins including corticosteroid binding globulin (CBG), and serum albumin; Only free cortisol is available to most receptors.
  • primary control of cortisol is the pituitary gland peptide, adrenocorticotropic hormone (ACTH). ACTH is in turn controlled by the hypothalamic peptide, corticotropin releasing hormone (CRH), which is under nervous control.

The information in this article is not meant to be medical advice.�Treatment for a medical condition should come at the recommendation of your personal physician.

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