ADRENAL GLANDS HORMONES

Transcription

1 ADRNAL GLANDS HORMONS Glands Cortex 80% mesoderm Mineralococorticoids Glucocorticoids (phenylethanolamine N- methyl transferase) A Sex Hormones Catecholamines Medulla 20% PNMT, N neuroectoderm N PNMT V Steroid Biosynthesis Cytochrome P 450 scc (CYP11A1, desmolase) Zona glomerulosa contains 18-OH but no cholesterol Mineralocorticoid Dehydroepiandrosterone Prenenolone 17α - OH Pregnenolone Progesterone17α - OH Progesterone Androstenedione 17β-HSD 11- Deoxycorticosterone 11- Deoxycortisol Corticosterone 18-OH 18-OH Corticosterone 18-HSD Glucocorticoid Cholesterol Testosterone strone ( 1 ) stradiol ( 2 ) Steroid nucleus Regulation of Glucocorticoid Secretion CRH Stimulates synthesis and secretion of Trophic effect Prolonged deficit atrophy of adrenal cortex Increases steroid synthesis Feedback to CRH Circadian regulation Feedback to CRH & Hormones of adrenal cortex Glucocorticoids Mineralocorticoids Sex hormones Lights Out Lights On Circadian (diurnal) ( secretion Life preserving actions Protect organism against acute and chronic stress 95% protein bound: CBG / SHBG / ABG / Albumin 13

2 Actions (1) Metabolic effects CHO (Diabetogenic) Gluconeogenesis utilization Insulin sensitivity Protein (Catabolic) Protein break down Lipid Lipolysis Redistribution of fat Food Adipose tissue Muscle Calories Triglycerides Selected sites Lipolytic H 4 Insulin 3 Free fatty acids 2 Glycogen Protein Liver precursors 1 2 Amino acids 3 Insulin Stimulate Protein Inhibit CVS effects Actions (2) - Stimulate cardiac contractility - Necessary for vascular response to CATs vasoconstriction - Maintain CF volume & capillary integrity - Mineralocorticoid effects increase renal Na + reabsorption & K + excretion cortisol B.P Actions (3) Neural effects - Necessary for fetal & neonatal neuron development - Influences behavior & cognitive function - Augments sympathetic actions Other ffects - Stimulates RBC production -Normalskeletal& cardiac muscle contraction - Collagen synthesis (Skin & blood vv ) - Fibroblast activity Fibrosis Actions (4) High dose High dose Stabilize lysosomes PG S, TX S, LT S Interleukin Capillary permeability Phagocytosis T-lymphocytes Suppress antibody Therapeutic Usage of Glucocorticoids Fever Anti-inflammation Anti-allergic Immuno-suppressant Actions (5) Bone protein matrix / Osteoblast GI Ca 2+ absorption ( Vit D action & synthesis ) Renal Ca 2+ excretion Glucocorticoids xcess Blood Ca 2+ PTH Abnormal secretion Trophic effect adrenal gland hyperplasia Stimulate glucocorticoids and adrenal androgens MSH-like activity in human High skin hyperpigmentation Osteoporosis Bone Resorption Bone Formation low skin hypopigmentation 14

3 Abnormal Glucocorticoids Secretion xcess Cushing s Syndrome (1 o & 2 o ) Cushing s Disease (2 o ) Deficit Addison s Disease (1 o adrenal insufficienncy high ) Cushing s Syndrome Cushing's Syndrome (1) Cushing's Syndrome (2) Appetite Insulin (insulin resistant) Protein breakdown ( protein structure of skin,muscle,bone) Fibroblast function GH truncal obesity diabetes mellitus connective tissue capillary fragility ecchymosis poor wound healing muscle wasting weakness osteoporosis growth retardation growth retardation Phagocytosis Mineralocorticoid effects Gastric acid & pepsin Nervous system High risk infection High risk infection hypernatrmia hypertension hypokalemia peptic ulcer peptic ulcer Personality change Steroid psychosis High xogenous Glucocorticoids Glucocorticoids Deficit (1) Stop exogenous cortisol Prednisolone(4) Dexamethasone (25) Suppress endogenous cortisol synthesis Susceptible to adrenal insufficiency Metabolic effects CVS impaired capillary integrity impaired vascular response to CATs weight loss hypoglycemia hypotension hypotension Life threatening especially when stress 15

4 0040-swf_effect_of_aldo.swf ffects Helps maintain water and salt balance by increases Na + reabsorption K + excretion H + excretion Regulation of Secretion Hemorrhage Upright posture Sodium deprivation Deficit activity Plasma K + Arterial pressure Na + to macula densa Kidneys are not able to regulate salt and water balance Blood volume and blood pressure drop (hypovolemic shock) crisis when severely stress Impaired renal excretion of K + & H + hyperkalemia metabolic acidosis Usually occurs with glucocorticoid deficit xcess Sex Hormones 1 0 = Conn s syndrome 2 0 = Renin-angiotensin Male Major Na + and water retention Hypertension Hypokalemia Metabolic alkalosis Hypocalcemic tetany Less than 5% Female of total androgen Sexual responsiveness Libido Sexual hair growth 16

5 Congenital Hyperplasia (CAH) Negative feedback secretion Pituitary Bilateral Hyperplasia nzyme defect Skin pigmentation Accumulation of cortisol precursors 1 Virilization 2 Precocious puberty Synthesis of cortisol ( + aldosterone) Congenital nzymatic Defect Severe cases -Die in utero (salt-loosing form) Mild cases - Virilized female infant/ adult - Precocious puberty in boy - crisis when stress Mineralocorticoid Prenenolone Progesterone 11- Deoxycorticosterone Corticosterone 18-OH Glucocorticoid 17α - OH Pregnenolone 17α - OH Progesterone 11- Deoxycortisol Dehydroepiandrosterone Androstenedione Testosterone Sympatho- System Neural crest Sympathogonia Neuroblast Pheochromoblast Ganglia cells Medullary Chromaffin cells (Pheochromocytes) xtra adrenal Chromaffin cells Splanchnic N Brain ganglia medulla Spinal cord N N nerve ending Catecholamine Synthesis & Secretion Medullary Hormones Catecholamines -N, Dopamine Opioid peptides -nkephalins OP N Circulation N 15% 85% Stimuli Hydroxylase Dihydroxyphenylalanine (DOPA) DOPA Decarboxylase OP DA Dopamine (DA) DH N DA Hydroxylase Norepinephrine (N) Chromaffin cell PNMT pinephrine () Sympatho- System Work hand in hand & N ~ 10% of sympathetic activity Increase after marked deviation of homeostasis circulating hormone N Fine regulation Neurotransmitter (local hormone) Intense stimulation circulation 17