Adrenal Gland Pt 2.docx

Zona fasciculata: (produces) glucocorticoides (cortisol) HPA-axis: hypothalamus (produces CRH) pituitary (produces ACTH) adrenal (produces cortisol)- axis Glucocorticoid production is stimulated by stressors such as: Low blood glucose Hypovolemia Emotional stress (fear or anxiety) Cortisol increases...

Zona fasciculata: (produces) glucocorticoides (cortisol) HPA-axis: hypothalamus (produces CRH) pituitary (produces ACTH) adrenal (produces cortisol)- axis Glucocorticoid production is stimulated by stressors such as: Low blood glucose Hypovolemia Emotional stress (fear or anxiety) Cortisol increases expression of genes that regulate: Metabolism Cardiovascular system Reproduction Growth Immune system Circadian (daily rhythm) or diurnal rhythm More cortisol is produced in the morning (while the night has increased melatonin production) Cortisol stimulating protein catabolism Amino acids (AA) mobilize from extrahepatic tissue (specifically from skeletal muscle or occasionally bones) Some AA act as substrates for making new enzymes while others act as substrates for gluconeogenesis Cortisol reducing cellular protein synthesis of body proteins Cortisol will decrease protein and RNA synthesis Long-term excessive cortisol release can lead to: Muscle wastage due to decline in muscle fiber synthesis Osteoporosis due to decreased bone formation Cortisol and stress Stress and diurnal rhythm impact the HPA-axis Stress is the biological response to internal or external stimuli or change in body homeostasis Examples of causes of stress: hypoglycemia, inflammation, physical trauma, emotional stress, pathogens Cortisol impact on lipid metabolism Cortisol will increase mobilization (break down) of fatty acids form adipose tissue. This will cause TAG to be broken into FFA (free fatty acids) and glycerol Cortisol will shift metabolism from glucose to fat. This makes the muscles prefer fat as an energy source as opposed to glucose Cortisol enhances oxidation of FFA in cells, causing decline in glucose transport into fats cells Symptoms: obesity Pot belly appearance due to decline in peripheral fat and increase in visceral (abdominal fat) In other words, FFA are being redirected from adipose tissue to the liver and abdomen to be used for energy. However, because there is a surplus of FFA, they also get stored here. This increases the visceral fat and results in a pot belly appearance and obesity Cortisol impact on carbohydrate metabolism Cortisol’s major goal is to increase glucose levels. Glucose levels will increase by increasing gluconeogenesis (GNG) and increasing glycogenolysis Cortisol stimulates the synthesis of enzymes used for GNG Cortisol mobilizes substrates from the extrahepatic tissue, increasing substrate concentration to be used for GNG Substrates: AA (from muscles and occasionally bones) and fat (glycerol- from the adipose tissue) Cortisol antagonizes (does the opposite of) insulin’s inhibitory effects on GNG and glycogenolysis Insulin’s major goal is to store glucose as glycogen Cortisol will potentiate (enhance) the actions of glucagon (hormone of starvation) and epinephrine on glucose metabolism by increasing glycogenolysis Cortisol has a “permissive effect” meaning that it’s presence allows for the actions of another hormone Cortisol impact on diabetes mellitus High cortisol levels can lead to diabetes mellitus (steroid diabetes) due to increased gluconeogenesis and decrease in glucose usage 10% of dogs with hyperadrenocorticism (Cushing’s disease) will also develop diabetes mellitus Prolonged administration of glucocorticoids can also cause diabetes mellitus Cortisol impact on the immune system Cortisol will: Stabilize lysosomal membranes causing declined release of proteolytic enzymes by damaged cells Decrease synthesis of (eicosanoids) prostaglandin and leukotrienes, causing decreased vasodilation, and therefore decreasing permeability and migration of WBC’s Decrease histamine secretion by mast cells Decrease phagocytosis and suppresses antibody formation Prevent (reduce) connective tissue (collagen) synthesis Ultimately, cortisol will suppress the immune system and decrease inflammation Cortisol inhibitory effects on things not required for survival Reproductive system impacts Inhibits various mechanisms of actions, causing decline in reproductive success Growth impacts Inhibits various mechanisms of actions, causing inhibition of insulin like growth factors (ISG-1) Cortisol impact on the cardiovascular system Cortisol will: Increase vascular smooth muscle sensitivity to vasoconstrictors like catecholamines Suppress release of vasodilators like nitrous oxide Help maintain blood pressure Zona reticularis: (produces) androgens Androgens are not significant, action-wise, in most animals. However, it will increase libido and secondary sexual characteristics for humans. Androgens are hormones that interact with male sex hormone receptors Androgen production is regulated by ACTH Cholesterol is a precursor molecule for androgens Step 1: Dehydroepiandrosterone (DHEA) is converted into androstenedione. Step 2: Androstenedione is released into the blood stream and travels to the testis or ovaries. Step 3: Based on location, androstenedione is converted into either estrogen or testosterone. Catecholamine synthesis (in the adrenal medulla) Step 1: Inside the chromaffin cell, L-tyrosine is converted into L-DOPA Step 2: Inside the cytosol (of the chromaffin): L-DOPA is converted into Dopamine Step 3: Inside a chromaffin granule, dopamine is converted into norepinephrine (NE) Step 4: NE goes to the cytosol and is converted into epinephrine (EPI) Step 5: EPI goes into a (chromaffin) granule for storage prior to it’s release NE exerts negative feedback on the pre-ganglionic sympathetic receptors Catecholamine metabolism Inside the liver and kidneys: Catecholamines are degraded by COMT (methylation via catechol-o-methyltransferase), and MAO (monoamine oxidase) systems Catecholamines are also excreted in urine as VMA Clearance half-life of: NE: 2-2.5mins EPI: 2mins Dopamine: 1min NE metabolism: Option 1 Step 1: NE uses MAO to convert into dihydroxymandelic acid Step 2: Dihydroxymandelic acid uses COMT to convert into VMA for urine secretion NE metabolism: Option 2 Step 1: NE uses COMT to convert into normetanephrine Step 2: Normetanephrine uses MAO to convert into VMA for urine excretion EPI metabolism: Option 1 Step 1: EPI uses MAO to convert into dihydroxymandelic acid Step 2: Dihydroxymandelic acid uses COMT to convert into VMA for urine secretion EPI metabolism: Option 2 Step 1: EPI uses COMT to convert into metanephrine Step 2: Metanephrine uses MAO to convert into VMA for urine excretion Catecholamine Actions (flight or fight response): EPI and NE will both increase energy availability and overall metabolism. This is useful during periods of acute stress so that the animal can adjust. Catecholamines bind to adrenoceptors GPCR (including; alpha 1, alpha 2, beta 1, and beta 2 receptors) Catecholamines will: Stimulate alpha receptors in arterioles of visceral organs, causing constriction of smooth muscle, resulting in restricted blood flow Increase heart rate and force of contractions for each heart beat, resulting in increased blood pressure Cause vasodilation of skeletal muscle and liver arterioles, causing an increase in glycogenolysis in the liver and muscles, as well as increased GNG in the liver which will increase available glucose Stimulate lipolysis in adipose tissue, increasing ATP produced from FFA within beta oxidation, and glycerol will enter GNG Increase basal metabolic rate Catecholamines binding to alpha 1 receptors will stimulate: Vasoconstriction Increased peripheral resistance Increased blood pressure Mydriasis (eye dilation) Mucosa decongestion Hyperglycemia Contraction of pilomotor muscles within the skin Catecholamines binding to beta 1 receptors will stimulate: Tachycardia Increased lipolysis Increased myocardial contractility Increased renin release Catecholamines binding to beta 2 receptors will stimulate: Vasodilation Increased peripheral resistance Bronchodilation Increased muscle and liver glycogenolysis Increased glucagon release Catecholamines binding to beta 3 receptors will stimulate: Thermogenesis and lipolysis within adipose tissue