STRESS ACTIVATED PATHWAYS Humoral pathway STRESS RAS pathway Limbic system Visceral brain Norepinephrine Endocrine Neuronal pathway Hypothalmus CRF 41 residues Renin Anterior pituitary Fight or flight ACTH 39 residues Angiotensin I & lI Adrenal cortex Adrenal cortex cortisol glycogen Aldosterone GR receptor increased Antinflammatory effects blood ← Sodium uptake cell death pressure
STRESS ACTIVATED PATHWAYS Humoral pathway STRESS Neuronal pathway RAS pathway Limbic system Visceral brain Endocrine Hypothalmus Anterior pituitary Adrenal cortex cortisol (-) (-) (-) CRF 41 residues ACTH 39 residues GR receptor Antiinflammatory effects cell death glycogen Fight or flight Norepinephrine Renin Angiotensin I & II Adrenal cortex Aldosterone Sodium uptake increased blood pressure
MAJOR NATURAL GLUCOCORTICOIDS OH OH HO OH HO Cortisol(hydrocortisone) OH Corticosterone OH Cortisone
MAJOR NATURAL GLUCOCORTICOIDS Cortisol (hydrocortisone) O OH O HO OH Corticosterone O OH O HO O OH O O OH Cortisone
BIOSYNTHESIS OF GLUCOCORTICOIDS o HO "OH HO cholesterol 17a-hydroxy 11B, 17a(OH)2-progesterone pregnenolone e f 0b OH HOCH2-O HOCH2=0 OH oH HO " OH cd HO pregnenolone o 17a-hydroxy 11-deoxycortisol Cortisol b. 17a-hydroxylase progesterone e OH c.5-ene-3β- hydroxy dehydrogenase o C, d d. 3-0X0-4.5-isomerase OH HOCH2YO e. 21-hydroxylase OH f. 11B-hydroxylase HO 17x,21(OH)2 pregnenolone Cortisone
BIOSYNTHESIS OF GLUCOCORTICOIDS HO HO O HO O OH O O OH O HOCH2 O OH O HOCH2 O HO OH O HOCH2 O O OH O O HO OH cholesterol pregnenolone 17a-hydroxypregnenolone 17a-hydroxyprogesterone 11-deoxycortisol Cortisol Cortisone 17a,21(OH)2 - pregnenolone 11b,17a(OH)2 -progesterone OH HO OH O b c,d e f e c,d f e b. 17a-hydroxylase c. 5-ene-3b-hydroxy dehydrogenase d. 3-oxo-4,5-isomerase e. 21-hydroxylase f. 11b-hydroxylase
GLUCOCORTICOID- METABOLISM OH OH Hydrocortisone Oxidation HO OH OH Cortisone o Oxidation/reduction Reduction OH COOH HO H OH HO -OH OH HO HO H 3-keto-A4 and 20-keto reduced Acid metabolites
GLUCOCORTICOID - METABOLISM O HO O OH OH O O O OH OH Cortisone Hydrocortisone Oxidation Reduction OH H OH HO HO HO H 3-keto-D4 and 20-keto reduced COOH OH OH H HO HO H Oxidation/reduction Acid metabolites