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Adrenal hormones Why stress about it? Adrenal gland • Really two separate glands • Cortex- Outer not essential to life – – – – Produces 3 categories of steroids mineralocorticoids -aldosterone Glucocorticoids-cortisol, corticosterone Sex steroids • Medulla- (inner) essential to life – Produces catecholamines epinepherine+norepinepherine Origin of Adrenal tissue and hormones • Steroids produced from mesodermally derived tissue • Cortex and gonads- derived from mesoderm • Medulla- derived from and develop with sympathetic ganglia Macroscopic anatomy • • • • Cortex and medulla regions only applicable to mammals Non mammals have medulla or cortex like regions Suprarenal or intrerrenal glands Chromafin tissue-medullary like tissue that produces catecholamines found in the abdomen Regulation • Medulla is regulated totally by nerves • Cortex is regulated totally by ACTH Microscopic anatomy • Mammals cortex - 3 regions – Zona glomerulosa – Zona faciculata – Zona reticularis • Z.G. produces mineralocorticoids and new cortical cells - can regenerate if damaged. • All three layers produce glucocorticoids – Z.F. and Z.R. produce the sex steroids. Microscopic anatomy • Medulla- contains lots of blood vessels and sinusoids. • Contains chromaffin tissue (produces catecholamines) • Regulation of the medulla is nervous. Hormone Chemistry • Cathecholamines • Epinepherine, norepinepherine, DOPA • Catechol-aromatic ring with alanine • Found in adrenal medulla,nervous tissue both sympathetic and parasympathetic systems • Precursors are phenylalanine - tyrosine- 3,4 DH Dopa- 3,4 DH, dopamine Metabolism • Liver, Kidney, and Target Tissue • COMT, MOA-breakdown catecholamine • Not avidly bound. Short 1/2 life Functions Of Catecholamines • Provide responses to acute and chronic stress -Fight or flight- adrenal medulla and Sympathetic NS • Massive CNS Stimulation-Anxious- Alert- Attentive • Quick stimulation of muscles, increase reflexes/strength Cardiovascular System • • • • Raise Heart Rate-epinephrine increase Cardiac Output- epinephrine increase Blood Pressure-epinephrine no effect, norepinephrine increase Peripheral Resistance-dilates skeletal muscle epinephrine-norepinephrine causes vasoconstriction Metabolic Effects • • • • • Fat Mobilization-(both) provide free fatty acids as energy source Major Diabetogenic Hormone Proteins Caloriogensis Epinephrine and norepinephrine work together Clinical applications of catecholamines Treat Anxiety, depression or mood disorders agonists -epinepherine analogs Catecholamine Regulation Adrenal Cortex • • • • Steroid Synthesis- all come from acetate and cholesterol C-18 Estranes (estrogens) C-19 Androstanes (Androgens) C-21 Pregnanes (progest, mineralcorticords, glucocorts Adrenal Cortex • Steroid Synthesis - emphasis on adrenal production • Two Important Synthetic Steroids - Dexamethasone, and Prednisone Pathways of adrenal steroidogenesis • • • • • • • Cholesterol Pregnenolone Progesterone Deoxycorticosterone Corticosterone 18-hydroxycorticosterone Aldosterone • • • • • Mineralocorticoids 17 hydroxypregnenalone 17 hydroxyprogesterone 11 deoxycortisol Cortisol • Glucocorticoids Adrenal Cortex • Adrenogenital Syndrome- alteration in one of these enzyme systems. Blocking of hydroxlases in corticosterone pathway results in orderly or over production of other pathways (androgens surge) • Glucocorticoids are 90% bound • Aldosterone is mainly free • Liver and Kidney primary targets Quiz Discuss the factors that regulate the secretion of catecholamines. Function of Adrenal Cortex Hormones • Mineralocorticoids – Aldosterone- regulates H2O and electrolyte balance (osmoregulation) – Active uptake of Na+ and H2O occurs – Mammals- Kidney tubules, Sweat, Salivary, Intestinal glands Regulation of adrenal cortical hormones • • • • Indirect influence from sympathetic nervous system Decrease in Na/Increase in K - raise aldosterone Decrease in ECF ( blood loss or dehaydration Triggered by angiotensin II Stress, anxiety, trauma Regulation of cortex • Chemical – Aldosterone, renin, Angiotensin I, II • Neural – Hardwiring to the JGA • Metabolites – K/Na • Chronotropic – Elevated day/lowered night Functions of Glucocorticoids • • • • • Primary effect is as metabolic regulator Maintain carbohydrate levels to supply the CNS Produce hyperglycemia Dec. uptake by non-essential tissues Stimulate gluconeogenesis Functions of Glucocorticoids • • • • • • Catabolize protein providing AA’s for gluconeogenesis Immunosuppressive Anti inflammatory,anti allergenic Catabolic to skeletal muscle Weakens bones (collagen) Inc. RBC’s and Platelets dec. WBC’s Regulation of glucocorticoids • Neural – Emotional stress, physical wounds, bacterial infection • Chemical (diagram) Regulation of glucorticoids General Adaptation Syndrome • Stress responses – Specific- heat-sweat, cold-shiver – Nonspecific- same no matter what the stimulus is but the degree can vary • Selye – Non specific stress elicits the following responses: General Adaptation Syndrome • Alarm reaction- fight or flight response,muscles tense, HR and BP increase • Resistance or adaptation-nervous and endocrine systems deal with stressor. dangerous if longterm. • Exhaustion-resistance drops, immunity suppression, depletion of energy reserves, stress related disease. General adaptation Syndrome General Adaptation Syndrome General Adaptation Syndrome