Adrenocortical Hormones Glucocorticoids Mineralocorticoids 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Adrenal Glands Suprarenal glands 5 gm Cortex 80% of gland Medulla Centrally located 20% of gland Related to sympathetic nervous system 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Secrete corticosteroid Synthesized from steroid cholesterol Have nearly similar chemical formula Slight differences in molecular structure Give them different functions 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Zona glomerulosa Outer most layer Secrete aldosterone Zona fasciculata middle layer of cortex Zona reticularis Innermost layer of cortex Glomerulosa Fasciculata Reticularis Medulla 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Zona fasciculata & reticularis Secrete cortisol & androgens Glomerulosa Fasciculata Reticularis Medulla 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Corticosteroids Mineralocorticoids Effect on electrolytes Glucocorticoids Exhibit important effect in increasing blood glucose conc Also affect fat, protein metabolism Androgens Sex hormones 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Structure Derivative of cholesterol Have 3 cyclohexyl rings( A, B, C) One cyclopentyl ring (D) 18 19 12 17 11 13 D 16 C 1 14 9 2 10 15 8 A B 3 5 4 7 6 Cyclopentanoperhydrophenanthrene 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Structure Adrenocortical steroids are of 3 types C21 steroids Have 2 –carbon side chains at position 17 C19 steroids Have a keto or hydroxyl group at position 17 C18 steroids In Addition to a 17 – keto or hydroxyl group Have no angular methyl group attached to position 10 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Structure Adrenal cortex secrete C21 and C19 steroids Most C19 steroids have a keto group at position 17 17 – ket0 – steroid C21 steroids that have a –OH group at position 17 in addition to side chain 17-hydroxycorticosteroids 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Structure C19 steroids have Androgenic activities C21 steroids have Mineralocorticoids effects N+, K+ excretion Glucocorticoids effect Glucose , protein, fat metabolism 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Synthesis Cholesterol ACTH Ang II pregnenolone Cortisol & sex steroids progesterone 11 -hydroxylase Deoxycorticosterone Cortisone Aldosterone synthatase, Ang II 18-hydroxycorticosterone Aldosterone synthatase Aldosterone 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Synthesis Acetate cholesterol pregnenolone 17-OH-pregnenolone progesterone 17-OH-progesterone cortisol Androgen aldosterone 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones S ynthesis OH CH2OH O 18 CH C=O 19 12 17 11 13 D 16 C Oxygen atom bound at carbon 18 This provides the mineralocorticoid activity 1 14 9 2 10 15 8 A B 3 5 4 7 6 Aldosterone 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Synthesis 21CH2OH CH3 C=O OH OH 12 17 11 13 19 D 16 C Presence of keto oxygen at C3 And hydroxylation at C11 , C21 1 14 9 2 10 15 8 A B 3 5 O 4 7 6 Cortisol 12/31/2018 Adrenal Cortex Hormones

Mineralocorticoid Activity Aldosterone Very potent, accounts for 90% of all activity Deoxycorticosterone 1/15th as potent as aldosterone Corticosterone Slight activity 9-fluorocortisol Synthetic, slightly more potent than aldosterone Cortisol Slight activity, but large quantity secreted Cortisone Synthetic, slight activity 12/31/2018 Adrenal Cortex Hormones

Glucocorticoid Activity Cortisol Very potent, 95% of total activity Corticosterone 4% of total activity Cortisone Synthetic, almost as potent as cortisol Prednisolone Synthetic, 4 times more potent than cortisol Methyl prednisolone Synthetic, 5 times more potent than cortisol Dexamethasone Synthetic, 30 times more potent than cortisol 12/31/2018 Adrenal Cortex Hormones

Transport & Fate of Adrenal Hormones Cortisol Combine with globulin Transcortin Cortisol binding globulin Also can combine with albumin About 94% transported in bound form; 6% in free form 12/31/2018 Adrenal Cortex Hormones

Transport & Fate of Adrenal Hormones Aldosterone Combine loosely with plasma protein About 50% is in free form 12/31/2018 Adrenal Cortex Hormones

Transport & Fate of Adrenal Hormones Both combined and free form Transported through out ECF Cortisol become fixed to target tissue within 1 or 2 hrs Aldosterone become fixed within about 30 min 12/31/2018 Adrenal Cortex Hormones

Transport & Fate of Adrenal Hormones Adrenal steroids degraded in liver Conjugated to glucoronides or sulfated to sulfate Then 25% excreted though bile 75% excreted through urine 12/31/2018 Adrenal Cortex Hormones

Functions of Glucocorticoids Affect metabolic systems for utilizing Proteins Carbohydrates Fats 95% of glucocorticoid activity of adrenal cortex result from Cortisol (hydrocortisone) 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Effects of Cortisol On carbohydrate metabolism Stimulate gluconeogenesis  Liver enzymes for Converting AA into glucose Activation of DNA transcription to form enzymes  Protein catabolism Mobilization of AA From extra hepatic tissues For gluconeogenesis 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Effects of Cortisol  Glucose utilization by cells Exert anti insulin effect Block glucose transport in muscle & adipose tissue Glucose intolerance Steroid diabetes Cortisol Indirectly inhibit activity of glycolytic enzymes Glucokinase, phosphofructokinase, pyruvate kinase 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Effects of Cortisol Glucocorticoids mobilize FA from Adipose tissue to liver Released metabolites inhibit glycolysis Glycerol is substrate for gluconeogenesis Glucocorticoids Associated with compensatory hyper insulinaemia 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Mechanism of Action Hormone Multiple effects of glucocorticoids triggered by Binding to receptors which Promote DNA transcription H-R complex H-R complex Ribosome DNA mRNA prot synthesis Nucleus Response 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Mechanism of Action Hormone Formation of mRNA Synthesis of enzymes Alter cell functions H-R complex H-R complex Ribosome DNA mRNA prot synthesis Nucleus Response 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Protein Metabolism Glucocorticoids enhance protein catabolism Skeletal muscle, extra hepatic tissues, protein matrix of bone Released AA transported to liver Converted to glucose 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Protein Metabolism Glucose production via gluconeogenesis Associated with  Urea production  Urinary nitrogen excretion Negative nitrogen balance Glucocorticoids Inhibit synthesis of protein 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Fat Metabolism Glucocorticoids are lipolytic Potentiate lipolytic actions of other hormones GH, catecholamines, glucagon, T3,T4 Favour FA mobilization From adipose tissue to liver 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Fat Metabolism FFA metabolized by liver -Oxidation Formation of ketone bodies Inhibit glycolysis Fructose 1,6 diphosphatase Activated by FA Pyruvate kinase , phosphofructokinase Inhibited by FA Glycolysis is inhibited, gluconeogenesis proceeds 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Fat Metabolism Glucocorticoids indirectly stimulate lipolysis by Blocking peripheral glucose uptake, utilization Inhibit re-esterification of FA in adipose tissue Inhibit the use of glucose 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Fat Metabolism Cortisol inhibit FA synthesis in the liver This effect is not observed in adipose tissue Overall effect Redistribution of body fat  In total body fat Trucal obesity 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Fat Metabolism Characteristic centripetal distribution of fat Accumulation of fat on central axis of body Deposition of fat on the face Moon face 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Fat Metabolism Deposition of fat in supra scapular region Buffalo hump Excessive fat distribution Pendulous abdomen 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Control of Secretion Limbic system Hypothalamus under the influence of higher centers Releases Corticotrophin releasing hormone (CRH) Hypothalamus CRH Negative feed back Adeno-hypophysis ACTH Adrenal cortex Plasma cortisol conc 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Control of Secretion Limbic system CRH acts on anterior pituitary Releases ACTH ACTH acts on adrenal cortex (zona fasciculata ( cortex) Releases cortisol Released into plasma Hypothalamus CRH Negative feed back Adeno-hypophysis ACTH Adrenal corte Plasma cortisol conc 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Control of Secretion Limbic system Conc of plasma cortisol Negative feedback inhibition Hypothalamus Anterior pituitary Hypothalamus CRH Negative feed back Adeno-hypophysis ACTH Adrenal corte Plasma cortisol conc 12/31/2018 Adrenal Cortex Hormones

(II) Mineralocorticoids Aldosterone Secreted by the cells of the zona glomerulosa Functions Increase Na+ by The kidneys, sweat glands, salivary glands, GIT Increase excretion of K+, H+ 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Mechanism of Action Site of action Cortical collecting duct Act on the P cells Contain Na+ channels Aldosterone Induces formation of proteins Increase the number of open channels ISF Lumen Na+ Na+ Na+ K+ 12/31/2018 Adrenal Cortex Hormones

Adrenal Cortex Hormones Mechanism of Action Aldosterone also Increase the number of Na-K ATPase molecules in the basal lateral membrane Aldosterone increase the exchange of sodium and potassium Na+ conservation in ECF K+ is excreted ISF Lumen Na+ Na+ Na+ K+ Na+ K+ H+ 12/31/2018 Adrenal Cortex Hormones

Control of Aldosterone Secretion ECF volume/electrolytes Blood volume Arterial BP 12/31/2018 Adrenal Cortex Hormones

Control of Aldosterone Secretion  K+ conc in ECF Leads to an  in aldosterone secretion K+ acts directly on the cells of zona glomerulosa Depolarizes cell membrane Opening of voltage gated Ca++ channels Ca++ move into the cell  aldosterone secretion 12/31/2018 Adrenal Cortex Hormones

Control of Aldosterone Secretion Renin angiotensin system  In ECF volume leads to a fall in blood pressure Kidneys produce Renin Leads to the formation of angiotensin II Angiotensin II acts on Zona glomerulosa cells to produce aldosterone 12/31/2018 Adrenal Cortex Hormones

Atrial Natriuretic Peptide (ANP) Synthesized by the cells of atria muscles  In plasma vol ( Na+ & H2O retention) Increase venous return Distension of atria Causes production of ANF 12/31/2018 Adrenal Cortex Hormones

Atrial Natriuretic Peptide (ANP) ANP inhibit production of Renin Aldosteron Leads to a reduction of Na+ by the nephrons and hence Increased Na+ excretion in urine 12/31/2018 Adrenal Cortex Hormones