Cross references;   Steroids    Steroid Actions      Glucocorticoids    
  Stress    ACTH    Lamprey Cortisol, etc.    Teleost Cortisol      
Cortisol & Testosterone & Serotonin   Cortisol & Behavior       

Cortisol (Wiki) 
    "Cortisol (hydrocortisone) is a steroid hormone, or glucocorticoid, produced by the adrenal gland.[1] It is released in response to stress and a low level of blood glucocorticoids.  Its primary functions are to increase blood sugar through gluconeogenesis, suppress the immune system, and aid in fat, protein and carbohydrate metabolism.
Cortisol is produced by the adrenal gland in the zona fasciculata, the second of three layers comprising the outer adrenal cortex. This release is controlled by the hypothalamus, a part of the brain. The secretion of corticotropin-releasing hormone (CRH) by the hypothalamus triggers pituitary secretion of adrenocorticotropic hormone (ACTH). ACTH is carried by the blood to the adrenal cortex, where it triggers glucocorticoid secretion.

Cortisol ... activates anti-stress and anti-inflammatory pathways.[3]

Changed patterns of serum cortisol levels have been observed in connection with abnormal ACTH levels, clinical depression, psychological stress, ...

Cortisol is released in response to stress, acting to restore homeostasis. However, prolonged cortisol secretion (which may be due to chronic stress or the excessive secretion seen in Cushing's syndrome) results in significant physiological changes.[7]

The decline in water excretion following a decline in cortisol (dexamethasone) in dogs is probably due to inverse stimulation of antidiuretic hormone (ADH or arginine vasopressin), which is not overridden by water loading
Cortisol works 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.

    Cortisol "
Inhibits secretion of corticotropin-releasing hormone (CRH), resulting in feedback inhibition of ACTH (Adrenocorticotropic hormone or corticotropin) secretion. Some researchers believe that this normal feedback system may become dysregulated when animals are exposed to chronic stress

Cortisol "Shuts down the reproductive system, resulting in an increased chance of miscarriage and (in some cases) temporary infertility. Fertility returns after cortisol levels return to normal[39]"  
In addition to cortisol's effects in binding to the glucocorticoid receptor, because of its molecular similarity to aldosterone it also binds to the mineralocorticoid receptor. Aldosterone and cortisol have a similar affinity for the mineralocorticoid receptor; however, glucocorticoids circulate at roughly 100 times the level of mineralocorticoids. An enzyme exists in mineralocorticoid target tissues to prevent overstimulation by glucocorticoids and allow selective mineralocorticoid action. This enzyme—11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2)—catalyzes the deactivation of glucocorticoids to 11-dehydro metabolites

The adrenal gland - Endocrinology - NCBI Bookshelf 
    Cortisol, like the thyroid Hormone T3, has potent metabolic effects on many tissues. These are essentially anabolic in the liver and catabolic in muscle and fat; the overall effect is to increase blood Glucose concentrations. 

Box 4.9  Diagram showing the major actions of cortisol on metabolism

Image ch4fb9.jpg
  • Cortisol stimulates the release of amino acids from muscle. These are taken up by the liver and converted to glucose.

  • The increased circulating concentration of glucose stimulates insulin release. Cortisol inhibits the insulin-stimulated uptake of glucose in muscle via the GLUT4 transporter.

  • Cortisol has mild lipolytic effects. These are overpowered by the lipogenic action of insulin secreted in response to the diabetogenic action of cortisol.

  • Cortisol also has varied actions on a wide range of other tissues (see text for details).   

From: Chapter 4, The adrenal gland

Cover of Endocrinology
Endocrinology: An Integrated Approach.
NOTE:  Click on the image to access the full text of the book. 

The Endocrine System (Goog)
    Glucocorticoids  From the above. 

Control of Cortisol Secretion    

Cortisol and other Glucocorticoids are secreted in response to a single stimulator: adrenocorticotropic hormone (ACTH) from the anterior Pituitary Gland. ACTH is itself secreted under control of the Hypothalamic peptide Corticotropin-releasing hormone (CRH). The central nervous system is thus the commander and chief of Glucocorticoid responses, providing an excellent example of close integration between the nervous and endocrine systems.

Virtually any type of physical or mental  Stress results in elevation of cortisol concentrations in blood due to enhanced secretion of  control of the Hypothalamic peptide Corticotropin-releasing hormone (CRH) in the Hypothalamus. This fact sometimes makes it very difficult to assess Glucocorticoid levels, particularly in animals. Observing the approach of a phlebotomist, and especially being restrained for blood sampling, is enough Stress to artificially elevate cortisol levels several fold!

Cortisol secretion is suppressed by classical negative feedback loops. When blood concentrations rise above a certain theshold, cortisol inhibits Corticotropin-releasing hormone (CRH) secretion from the Hypothalamus, which turns off  ACTH secretion, which leads to a turning off of cortisol secretion from the Adrenal Cortex. The combination of positive and negative control on Corticotropin-releasing hormone (CRH) secretion results in pulsatile secretion of cortisol. Typically, pulse amplitude and frequency are highest in the morning and lowest at night.

  ACTH  binds to Receptors in the plasma membrane of cells in the zona fasiculata and reticularis of the  Adrenal Cortex. Hormone-Receptor engagement activates adenyl cyclase, leading to elevated intracellular levels of cyclic AMP which leads ultimately to activation of the enzyme systems involved in biosynthesis of cortisol from cholesterol."    


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