Cortisol (Hydrocortisone) Michael Monrean

Cortisol Cortisol is a steroid hormone derived from cholesterol. When used as a synthetic made drug it is referred to as hydrocortisone. Steroid hormones can be grouped into two classes 1. Corticosteroids Produced in the adrenal cortex 2. Sex Steroids Produced in the gonads or placenta Cortisol is classified as a corticosteroid Within these two classes there are multiple types depending on the receptors that the steroid binds to. Cortisol is thus classified as a glucocorticoid

Glucocorticoid Glucocorticoid (GLUCOse + CORTex + sterOID) Named for their role in glucose metabolism, where they are synthesized (adrenal cortex), and for their structure Anti-inflammatory Allergy Suppressant Immune Suppressant Released in response to stressors or low blood glucose Best known for their temporary increase in energy production from fight or flight response

Hypothalamopituitary adrenal (HPA) axis: Negative Feedback Glucocorticoids, Catecholamines, etc.. Muscle: Net loss of amino Acids (glucose) Liver: Deamination of proteins into amino acids, gluconeogenesis (glucose) Fat Cells: Free fatty acid mobilization Heart rate: Increased Immune system: altered External Stressors Posterior Pituitary Gland Hypothalamus Anterior (-) CRH ACTH Glucocorticoids, Catecholamines, etc.. Adrenals Kidney CRH = Corticotropin Releasing Hormone ACTH = Adrenocorticotropic Hormone Released from zona fasciculata

Steroidogenesis ACTH increases the concentration of cholesterol in the inner mitochondrial membrane, via regulation of the steroidogenic acute regulatory protein. It then stimulates the rate limiting step in cortisol synthesis in which cholesterol is converted to pregnenolone and catalyzed by side chain cleavage enzyme.

Cortisol C21H30O5

Glucocorticoid Receptor Effect cell by binding to the GR When bound, activated GR complex upregulates the expression of anti-inflammatory proteins in the nucleus (transactivation) Down regulates the expression of pro-inflammatory proteins in the cytosol by preventing translocation of many transcription factors from the cytosol into the nucleus (transrepression) Allows/disallows gene expression of certain transcription factors Play an important role in pulmonary maturation during fetal development  surfactant

GR complex moves into the cell to promote metabolic changes.

Effects of Cortisol Release Metabolic Response Cortisol stimulates gluconeogenesis and glycogenolysis in the liver and the muscles. Deamination of proteins into amino acids Extreme conditions may lead to proteolysis Glycogen to glucose and glucose-1-phosphate Immune Response Prevents release of substances in the body causing inflammation Treats conditions resulting from over activity of B-cell mediated antibody response i.e. inflammatory diseases such as eczema, rheumatoid arthritis, allergies Prevents proliferation and growth of T-cells With large exposure can weaken the immune system

Additional Effects Cortisol reduces bone formation by reducing Ca2+ absorption in the small intestine Long term exposure = possible osteoperosis Down regulates formation of collagen Important connective tissue. Effected by deleterious effect of immune system Negative effect on wound healing Acts as a diuretic Effects electrolyte balance by increasing glomerular filtration rate and plasma flow Consequently promotes potassium excretion and sodium retention Can effect memory retrieval and long term memory Works with adrenaline to produce emotional flash bulb memories

Diurnal Release Cycle There exists a normal release cycle in humans At highest levels early in the morning At lowest levels 3-5 hours after sleep onset Cycle believed to be regulated by light/dark cycle and information sent to suprachiasmatic nuclei of the hypothalamus via the retina. Important to receive adequate sleep so as not to be overexposed to higher cortisol levels

Cortisol Disorders Cushing’s Syndrome - high corticosteroid levels in the blood - changes in protein and carbohydrate metabolism - buffalo hump or moon face - free fatty acids mobilized to periphery Addison’s Disease or Nelson’s Syndrome - inadequate secretion of glucocorticoids - hypoglycemia, Na+ and K+ imbalance, dehydration, hypotension, rapid weight loss and general weakness - tints or shades of deep amber or brown skin (due to the stimulation of melanocytes from high ACTH secretion). This results from inadequate negative feedback from low glucocorticoid levels - John F. Kennedy had Addison’s Disease