The Mul(ple Roles of the Adrenal Glands in Human Physiology. Moe Goodman September 11, 2014
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1 The Mul(ple Roles of the Adrenal Glands in Human Physiology Moe Goodman September 11, 2014
2 Gross and Microscopic Anatomy of the Adrenal Gland
3 Principal Hormones of the Adrenal Glands Zona Glomerulosa HO CH 2 OH O C=O C Zona Fasciculata O Aldosterone CH 2 OH C=O HO OH O Cortisol O = Zona Re(cularis HO Dehydroepiandrosterone Medulla Epinephrine
4 Synthe(c Pathways of the Principal Adrenal Steroids Cholesterol Progesterone Pregnenolone 11- Deoxycor(costerone 17α- Progesterone Dehydroepiandrosterone Cor(costerone 11- deoxycor(sol Aldosterone Cor(sol
5 Secre(ons of the Adrenal Cortex are Necessary for Sustaining Life Mineralocor*coids directly regulate sodium and potassium balance and indirectly regulate body fluid balance. Glucocor*coids directly and indirectly regulate energy metabolism regulate immune responses facilitate the body s ability to cope with stress
6 Glucocor*coids Mineralocor*coids Androgens
7 Therapy mg/day Therapy mg/day Effects of Aldosterone in a Healthy Young Man 6 0 Aldosterone Aldosterone aldosterone Potassium Excretion mg/day Sodium Excretion meq/day Weight in Kg
8 Targets of Sodium Conserving Effects of Aldosterone Sweat Glands Kidney Aldosterone Salivary Glands Colon
9 Aldosterone Increases the Abundance of Sodium and Potassium Channels on the Luminal surfaces of Tubular Cells Na + Na + E Na C 2K + 3Na + K + K + ROMK Cortical Collecting Duct
10 General Scheme of Steroid Hormone Ac(on
11 Physiological Signals Governing Aldosterone Secre(on h Plasma Potassium Atrial Natriure(c Pep(de i Extracellular Fluid volume Heart Conver(ng enzyme
12 Regula(on of Aldosterone Secre(on Blood volume (- ) Renin/Angiotensin Blood Volume Plasma Potassium Aldosterone (- ) Sodium Retention Plasma Potassium
13 Extra- Adrenal Ac(va(on and Inac(va(on of Cor(sol H O C H 2 O H C = O OH H S D I H S D I I C H 2 O H C = O O OH O C o r t i s o l ( A C T I V E ) H S D I O C o r t i s o n e ( I N A C T I V E )
14 Cor(sol Receptors in Some Target Tissues Are Exposed to Very High Concentra(ons of Cor(sol Kidney Cor*sone target Target cells Cor*sone Adrenal Cortex Cor*sol Hormone receptor Cor*sol Receptor DNA Biological effects
15 Cor(sol Has Many Global and Tissue- Specific Ac(ons 1. Metabolic Maintains blood glucose through ac(ons on liver, adipose (ssue, and muscle 2. An*- inflammatory Counters inflammatory responses of lymphoid and connec(ve (ssues and circula(ng cells 3. An*- stress Protects against environmental challenges through suppor(ng and enhancing (ssue func(ons
16 Direct Effects of Cor(sol on Energy Metabolism Protein degradation Protein synthesis Glucose utilization Sensitivity to insulin amino acids Glycogen storage Gluconeogenesis Activity of enzymes Amount of enzymes Muscle Cortisol Liver Glucose Lipolysis Glucose utilization Sensitivity to insulin glycerol Adipose tissue
17 Cor(sol Poten(ates the Ac(ons of Other Hormones
18 Cor(sol is Required for Differen(a(on of Adipocytes Preadipocyte GH IGF-I Mitogenesis Other Growth Factors Growth Arrest (Commitment) Insulin Cortisol Mature Adipocyte Differentiation Insulin Cortisol Lipid Accumulation Insulin Cortisol
19 Cor(sol Has Many Global and Tissue- Specific Ac(ons 1. Metabolic Maintains blood glucose through ac(ons on liver, adipose (ssue, and muscle 2. An*- inflammatory Counters inflammatory responses of lymphoid and connec(ve (ssues and circula(ng cells 3. An*- stress Protects against environmental challenges through suppor(ng and enhancing (ssue func(ons
20 An(- inflammatory Effects of Cor(sol Inflammatory S(mulus Phospholipase A 2 Membrane Phospholipids Annexin 1 Cor*sol Arachidonic Acid Cyclooxygenase 1 & 2 Lipooxygenase Prostaglandins Leukotrienes Pain Heat Redness SwellingFunc(on Loss of Immune Cell Ac(va(on
21 Immunosuppressive Effects of Cor(sol Immune Complexes Interleukins Inflammatory mediators Macrophages Cor*sol TNFα, IL6 IL8, etc. Interleukin 1 T Cell Interleukin 2 T Cell prolifera(on B Cell prolifera(on An(body Produc(on
22 Effects of Interleukin I Mitosis Fever IL-2 Macrophage Sleep T Lymphocytes CNS Chemotaxis Neutrophils IL-1 Endothelial Cells Prostaglandins PG, LT Leukotrienes Bone and Cartilage Prostaglandins PG Lysosomes Muscle Prostaglandins PG Lysosomes Fibroblasts Mitosis Collagenase release Protein degradation Protein degradation
23 Cor(sol Breaks the Posi(ve Feedback Cycle of the Immune Response IL- 2 T Lymphocytes (- ) IL- 1 (- ) Cortisol (- ) z Ac(vated T Lymphocytes Macrophage IFN- γ
24 Cor(sol Has Many Global and Tissue- Specific Ac(ons 1. Metabolic Maintains blood glucose through ac(ons on liver, adipose (ssue, and muscle 2. An*- inflammatory Counters inflammatory responses of lymphoid and connec(ve (ssues and circula(ng cells 3. An*- stress Protects against environmental challenges through suppor(ng and enhancing (ssue func(ons
25 Injury Worry Jet Lag Illness Pain Fear Overwork Emo(onal Distress Environmental Toxins Exams Allergies Drug Abuse
26 The Pituitary and Hypothalamus
27 Regula(on of Cor(sol Secre(on stress time of day hypothalamus (+) AVP CRH (+) (-) pituitary (-) cortisol ACTH (+) adrenal cortex
28 Influence of the Immune System on Cor(sol Secre(on hypothalamus (+) (+) inflammatory cytokines pituitary immune system (+) (-) cortisol (+) ACTH adrenal cortex
29 Consequences of Excessive Cor(sol (Cushing s Disease) Emotional Disturbances Buffalo Hump Hypertension Thinning of the skin Thin arms and legs (muscle wasting) Abdominal Stria Cataracts Moon Face with red cheeks (plethora) Increased abdominal fat (truncal obesity) Avascular necrosis of femoral head Easy bruising Also: Osteoporosis i glucose tolerance (diabetes) Muscle weakness h susceptibility to infection Poor wound healing
30 Average Concentra*ons of DHEAS in Blood Throughout Life Adrenarche Puberty Birth DHEAS (nmol/l) Fetal Period years of age
31 DHEAS is a Precursor of Testosterone and Estradiol O = O SO 3 Dehydroepiandrosterone Sulfate (DHEAS) sulfatase O = O = OH HO Dehydroepiandrosterone (DHEA) 3 β -HSD O Androstenedione (Andro) 17 β -HSD O Testosterone P450 arom P450 arom O =! OH 17 β -HSD HO Estrone HO Estradiol 17β
32 DHEA Does NOT Feedback to Inhibit ACTH Secre(on CRH ACTH (-) Pregnenolone Cortisol DHEAS
33 Fright, Fight or Flight Response Hastens Blood Clogng Ac(vates Fear Defa(gues Muscle Dilates Pupils Heart Rate Force of Contrac(on Cardiac Output Insulin secreton h Glucagon secre(on Contracts or Relaxes Blood Vessels shiiing flow to working muscles and skin Fahy Acid Release from Adipose (ssue Relaxes Bronchioles Hepa(c Glucose produc(on i Diges(ve Ac(vity i Blood flow
34 Independent Secre(on of Epinephrine and Nor Epinephrine Plasma Catecholamine Concentration (pg/ml) Epinephrine Norepinephrine M i n u t e s b e f o r e o r a f t e r i n s u l i n i n j e c t i o n
35
36 Overall Response of the Adrenal Glands to Environmental Challenges
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