ADRENOCORTICAL HORMONES DR. AYISHA QURESHI MBBS, MPhil

THE ADRENAL GLANDS 2 in number Each weighs about 4 gms Each lies at the superior pole of the 2 corresponding kidneys. Each is composed of 2 distinct parts: - Adrenal cortex - Adrenal medulla

Reticularis Androgens Cortex Medulla ADRENAL GLAND Glomerulosa (15%) Mineralocorticoids Fasciculata (75%) Glucocorticoids Reticularis Androgens Medulla

PROPERTIES All Adrenocortical Hormones are: 1. Derivatives of cholesterol 2. Synthesized in the mitochondria & ER 3. Degraded in the liver & excreted in the bile, faeces & thru the kidneys. 4. Lipophilic & so carried bound to plasma proteins

Adrenocortical hormones Mineralocorticoid ALDOSTERONE Carried by Albumin Glucocorticoid CORTISONE Carried by Transcortin Androgens DHEA Carried by albumin

ALDOSTERONE

Synthesis: Transport: Half life: Derivative of cholesterol in the mitochondria & ER Transport: Bound to ALBUMIN! But only about 60% Half life: Thus shorter half life about 20 minutes! ALDOSTERONE Is a mineralocorticoid so called because of its effect on the minerals of the body MOA: by combining with cytoplasmic receptors and the hormone-protein receptor enters the nucleus to cause changes.

ACTIONS OF ALDOSTERONE ↑ Na Reabsorption ↑ K excretion ↑ Water reabsorption ↑ H ion excretion in exchange for Na SITE: Kidneys+ sweat +salivary glands+ Intestines

ACTIONS OF ALDOSTERONE

Regulation of Aldosterone Secretion: ↑K plasma conc. ↑Aldosterone A very potent effect!! ↑ Activity of Renin- Angiotensin system ↑ Aldosterone ↑ Na plasma conc. A mild effect!!

POINT TO REMEMBER: ACTH from the Anterior pituitary is necessary for Aldosterone secretion but has little effect in controlling the rate of secretion!

Question: What is Pressure Natriuresis & Pressure Diuresis?? A rise in arterial blood pressure causes increased excretion of both salt and water which is called Pressure Natriuresis & Pressure Diuresis.

Aldosterone Escape Excess Aldosterone secretion ↓ Na & water retention Increased blood volume Pressure Natriuresis & Pressure Diuresis Salt & water excretion returns to normal This is called Aldosterone Escape

What happens if Excess Aldosterone secretion? Hypokalemia (2mEq/L) Severe muscle weakness Effect on K conc. (normal levels: 4.5mEq/L) Hydrogen ion conc. decreased Mild Alkalosis Effect on Hydrogen ion conc.

CORTISOL

Cortisol is a Glucocorticoid so called because of its effect on glucose. It is also a derivative of cholesterol. About 99% cortisol binds to the plasma proteins esp. a globulin called cortisol binding globulin or Transcortin. Because most of the cortisol is in bound form, thus, it has a relatively long half-life of 60-90 minutes. MOA: thru combination with the receptors in the cytoplasm, which forms the hormone-receptor complex that enters the nucleus and causes protein synthesis.

ACTIONS OF CORTISOL 1. METABOLISM 2. STRESS & INFLAMMATION 3. BLOOD CELLS

CHO METABOLISM 1. Increased Gluconeogenesis 3. ADRENAL DIABETES Increased Gluconeogenesis Decreased Glucose Utilization 2. Increased Glycogen stores + Decreased Utilization of Glucose As there is Increased Glucose production in the liver Depressed oxidation of NADH to form NAD+(without this step NO Glycolysis) 1. Increased Gluconeogenesis a. Increasing the activity of enzymes needed & their DNA transcription b. Increased mobilization of AA from extrahepatic sites mainly muscle

PROTEIN METABOLISM Reduction in Cellular proteins ↑Catabolism to ↓ all body protein stores except liver By ↓AA transport into extrahepatic tissues By ↓ formation of RNA & thus proteins in all cells Reduction in Cellular proteins Everywhere in the body there is ↑ protein catabolism Paradoxically, there is ↑ AA transport into Liver cells for Gluconeogenesis ↑ Plasma protein formation in the Liver (for transport of cortisol) Increases Liver & Plasma Proteins

POINT TO NOTE: ↑Glucose + ↑Glycogen ↑ Protein catabolism ↑ AA transport into the Liver ↑ Plasma Protein synthesis ↓ AA transport into extrahepatic cells Most of the actions of Cortisol on metabolism are brought about by their ability to: mobilize AA from peripheral tissues WHILE SIMULTANEOUSLY increasing AA transport & concentration in the liver along with the enzymes needed for Gluconeogenesis

Fat Metabolism: Mobilization of FA ↑ conservation of Glucose & Glycogen Shifts the energy utilization substrate to FAT ↑ oxidation of Free fatty acids

Fat Metabolism Mobilization of fatty acids from all tissues Strange Obesity caused by Excess Cortisol: Moon face & Buffalo Hump What is the cause??

ROLE IN STRESS & INFLAMMATION Its secretion INCREASES in stress. It has anti-inflammatory effects: Blocks early stages of inflammation preventing it from starting If inflammation already started then it causes its rapid resolution & hastens healing. Blocks the inflammatory response to allergic reactions

Role in Inflammation How does it help in resolution of healing? Cortisol stabilizes the lysosomal membranes as a primary effect. Cortisol decreases the permeability of the capillaries as a secondary effect. Cortisol decreases both migration of White blood cells & phagocytosis of the damaged cells in the inflamed area. Cortisol suppresses the immune system, esp. decreasing the lymphocyte reproduction. Cortisol reduces fever as it decreases the release of interleukin-1 from the WBC.

Role in Autoimmune diseases Certain diseases respond well to Cortisol given as “steroids”: Rheumatoid arthritis Rheumatic fever Acute Glomerulonephritis All these diseases are characterized by severe local inflammation and the harmful effects are caused by the inflammation itself and not by the disease. When cortisol is given, then the inflammation subsides within 24 hours. This prevention of the damaging effects of the inflammation alone can be a life saving measure.

Effect on Blood Cells & Immunity 1. Decreases Eosinophils 2. Decreases Lymphocytes & antibodies 3. Atrophy of Lymphoid tissues 4. Decreases T-cells IMMUNOCOMPROMISED PATIENT 5. Increased RBCs

Regulation of cortisol secretion

Major control is brought about by ACTH (Adrenocorticotropic hormone) also called Corticotropin or Adrenocorticotropin. - Large peptide - M.w: 39 aa - secreted by the anterior pituitary gland

Hypothalamus (paraventricular cells) ↓ CRH (peptide with 41 aa) Hypophsyial- Hypothalamic portal system Anterior Pituitary ACTH Adrenocortical cells Increased cAMP Activates the intracellular enzymes esp. Protein kinase A Conversion of cholesterol to pregnenolone (rate limiting step for all adrenocortical hormone syn.)