Topic 10-Cortisol-S_2011

Topic 10-Cortisol-S_2011 - 10. Cortisol & the stress...

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Click to edit Master subtitle style 10. Cortisol & the stress response A. Adrenal anatomy & cortisol biosynthesis B. Signaling mechanism C. Role in stress & metabolism D. Regulation E. Role as a drug
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Let’s talk n Adrenal hormones respond to stress n What is stress? n Physiologic responses ¨ Metabolic ¨ Immune n CNS integration stress 22
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Humans are exposed to many n Often >1 stress n Integrated response n Endocrine system maintains homeostasis 33 Starvation (hypoglycemia) Hypothermia Fear Thirst Emotional (depression) Studying for Endocrinology exams Infection Injury Physical exertion
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Adrenal hormones n Cortisol ¨ Steroid ¨ “Glucocorticoid” ¨ Regulates metabolism n Aldosterone ¨ Steroid ¨ “Mineral corticoid” ¨ Regulates blood ion balance n Androgens n Epinephrine O H C H C H2 H N O H H O C H3 H O 44
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Anatomy of the adrenal gland kidne y Adren al gland capsul e Zona glomerul osa Z. fasciculata Z. reticularis Medull a Cortex =Zona glomerulosa, fasciculata, & reticularis; plus the capsule Aldostero ne Cortisol Epinephri Capsular artery Medullary vein ST ER OI DS ma de in CO RT EX Androgen s 55
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Review of steroid biosynthesis n Cholesterol precursor ¨ Major source: LDL ¨ Minor: synthesized de novo n Steroidogenesis ¨ Lipophilic substrate ¨ Molecular oxygen n Specialized enzymes: the cytochromes P450 ¨ Complexed with iron-containing proteins and NADH ¨ Electron transfer ¨ 2740 enzymes in 109 families 66
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Most steroid synthesis starts with a common pathway HO Side Chain Cleavage  StAR Steroid acute regulatory LDL receptor LDL HO O Pregnenolone HO 5 4 3 2 1 O C O R Cholester ol ester in lipid droplets 77
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Cortisol synthesis by multiple pathways in the Zona fasciculata 3 β - hydroxysteroid dehydrogenase 21 α hydroxylase 11 Pregnenolone Progesterone 11-Deoxy- corticosterone Corticosterone 11-Deoxycortisol 17 α -Hydroxy- progesterone 17 α -Hydroxy- pregnenolone 17 α - hydroxylase Cortisol 88
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Cortisol is a steroid, therefore we n
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Topic 10-Cortisol-S_2011 - 10. Cortisol & the stress...

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