Adrenal Gland 2 2024 Ross University PDF

Cellular Biology & Homeostasis ADRENAL GLAND - part 2 VP 2024 Clara Camargo, DVM 1. Define glucocorticoids and explain their synthesis and secretion 2. Understand the negative feedback mechanisms of the HPA axis (cortisol) 3. List the main effects of cortisol on the metabolism of protein, lipids and...

Cellular Biology & Homeostasis ADRENAL GLAND - part 2 VP 2024 Clara Camargo, DVM 1. Define glucocorticoids and explain their synthesis and secretion 2. Understand the negative feedback mechanisms of the HPA axis (cortisol) 3. List the main effects of cortisol on the metabolism of protein, lipids and carbs 4. Understand how cortisol affects different tissues (skeletal muscle, liver, adipose tissue and immune system) 5. Understand the synthesis and significance of adrenal sex hormones 6. Explain the characteristics of the adrenal medulla 7. Describe the synthesis of catecholamines 8. Briefly explain the metabolism and elimination of catecholamines 9. List the main types of adrenergic receptors 10. Understand the overall metabolic effects of the catecholamine hormones (EPI and NE) MINERALO CORTICOIDS GLUCO CORTICOIDS Main one: Main ones:  Aldosterone  Cortisol  Corticosterone SEX STEROIDS  Androgens CATECHOLAMINES  Epinephrine  Norepinephrine Regulation HPA axis CORTISOL increases the expression of genes Hypothalamic (CRH) that will regulate: Pituitary (ACTH) Adrenal (cortisol) Metabolism Immune system Cardiovascular function Growth In response to stressors  low blood glucose (glucocorticoid!)  hypovolemia  emotional stressors (fear, anxiety) Reproduction Circadian or Diurnal rhythm → higher blood concentrations of cortisol in morning than afternoon/evening “Stress” Biological response to external or internal stimuli; or a body's reaction to change to maintain homeostasis Hypoglycemia  Stress  Diurnal rhythm Inflammation Influencing the HPA axis Pathogens Physical trauma, hypotension Emotional stress Steroid hormones (lipophilic) bound to plasma proteins for transport in the blood  Corticosteroid-binding globulin (CBG) transcortin  Albumin Free cortisol binds to receptors in cytosol H-R complex migrates to the nucleus Stimulates or inhibits expression of specific genes Cortisol transport 75% bound to transcortin 15% bound to albumin 10% unbound (free state) Stimulate catabolism of proteins  Mobilization of amino acids from the Reduces cellular protein synthesis (body proteins) extrahepatic tissues  Decreases RNA and protein synthesis  Mainly from skeletal muscles (to a lesser  If long-term increased release of cortisol: extent from the bones)  AA serves as substrate for enzyme manufacturing  AA serves as substrate for gluconeogenesis Decrease muscle fiber synthesis → can cause muscle wastage Decreased bone formation can → cause osteoporosis  Increase mobilization of fatty acids from adipose tissue (TAG → FFA + Glycerol)  Shift the metabolism from glucose to fat utilization Can cause obesity  Enhance the oxidation of FFAs in cells  Reduced glucose transport into fat cells Depletion of peripheral fat while increasing visceral (abdominal) fat – “potbelly” → redirects FFA from adipose tissue to liver and abdomen Blood Sugar → increased gluconeogenesis (GNG) and glycogenolysis  Stimulates synthesis of enzymes involved in GNG  Mobilizes substrates from the extrahepatic tissues for GNG  AA → mainly from muscle (and bones to a lesser extent)  Fat (glycerol) → from adipose tissue  ↑ Substrate for GNG  Antagonizes insulin’s inhibitory effect of GNG and glycogenolysis in the liver ↑ Cortisol levels can cause Diabetes Mellitus (steroid Potentiates the action of glucagon and diabetes) epinephrine on glucose metabolism  Increased gluconeogenesis + reduction in glucose  Recall: glucagon (hormone of “starvation”) and epinephrine → ↑ glycogenolysis (catabolism of glycogen)  Permissive effect (the presence of one hormone enables another hormone to act) utilization* *FYI Decrease GLUT 4 translocation in skeletal muscle leading to insulin resistance  About 10% of dogs with hyperadrenocorticism (Cushing’s disease) also develops Diabetes Mellitus  Prolonged administration of glucocorticoids can cause steroid diabetes Main substrates: AA from protein catabolism NEFAs from adipose tissue Stabilizes lysosomal membranes Decreasing release of proteolytic enzymes by damaged cells immune system ↓ synthesis of prostaglandins and leukotrienes ↓ vasodilation, permeability and white blood cell migration ↓ secretion of histamine by mast cells ↓ phagocytosis and suppresses antibody formation Prevents connective tissue synthesis inflammation Cortisol inhibits secondary functions not necessary for survival  Reproductive system Various mechanism of actions → Reduces reproductive success  Growth Various mechanism of action → i.e., inhibiting insulin-like growth factor 1 (IGF-1) Cardiovascular system:  Increases the sensitivity of vascular smooth muscle to vasoconstrictors (i.e., catecholamines)  Suppresses the release of vasodilators (i.e., nitrous oxide)  Helps maintain blood pressure Adrenal insufficiency = Addison’s Disease Shieldmypet.com  Hyperactive adrenal cortex  Rounded race and obesity  Thin, frail skin  Poor wound healing  Hypoactive adrenal cortex  Decreased appetite, weight loss  Cold intolerance  Stress susceptibility MINERALO CORTICOIDS GLUCO CORTICOIDS Main one: Main ones:  Aldosterone  Cortisol SEX STEROIDS  Androgens CATECHOLAMINES  Epinephrine (=adrenaline)  Norepinephrine  Corticosterone Also produces some glucocorticoids Androgens are hormones that interact with male sex hormone receptors  Dehydroepiandrosterone (DHEA) Androgens’ production is regulated by ACTH  DHEA → androstenedione → released into the blood stream → testis or ovaries to produce testosterone and estrogens Less active than testosterone Adrenal androgens action is not significant in most animals (mostly contribute to increase libido and secondary sexual characteristics in humans) https://www.researchgate.net/figure/Synthesis-of-steroid-hormones-in-theadrenal-cortex-Synthesis-of-the-adrenal-steroid_fig1_231614936 MINERALO CORTICOIDS GLUCO CORTICOIDS Main one: Main ones:  Aldosterone  Cortisol  Corticosterone SEX STEROIDS  Androgens CATECHOLAMINES  Epinephrine (=adrenaline)  Norepinephrine Short-term (acute) stress Fight or flight response Chromaffin cells → neuroendocrine cells* *modified post-ganglionic sympathetic motor neurons, lack dendrites and axons Acetylcholine from pre-ganglionic sympathetic neurons → binds to nicotinic receptors on the chromaffin cells → secretion of catecholamines *FYI Neuropeptide pituitary adenylate cyclaseactivating polypeptide (PACAP) has been found to be required for stress-induced catecholamine secretion Catecholamines:  EPI (epinephrine) 80%  NE (norepinephrine) 20% 1. Inside of the chromaffin cells → Ltyrosine is converted to L-DOPA NE → exerts negative feedback at the pre-ganglionic sympathetic receptors  by the enzyme tyrosine hydroxylase 2. L-Dopa → dopamine in the cytosol 3. Dopamine → Norepinephrine  within the chromaffin granules  by the enzyme dopamine beta-hydroxylase 4. NE → to cytosol → Epinephrine 5. Epinephrine → granules for storage before release pre-ganglionic sympathetic neurons  Liver and kidney metabolism degraded primarily by the COMT (methylation via catechol-O-methyltransferases) and MAO (monoamine oxidase) system  Excreted in urine (as VMA) Clearance half-life (minutes) Norepinephrine: 2-2.5 Epinephrine: 2 Dopamine: 1 EPI and NE → Increase energy availability and overall metabolism allowing animals’ adjustments to situations involving acute stress  Bind to adrenoceptors GPCR on target tissues Major types of adrenergic receptors  Alpha (α) → α1 and α2  Beta (β) → β1 and β2  Stimulation of alpha receptors in the arterioles of most visceral organs causing: contraction of arteriolar smooth muscle → restricts blood flow  ↑ heart rate and force of contraction of each heartbeat raises blood pressure  Cause vasodilation of skeletal muscle and liver arterioles ↑ glycogenolysis in liver and muscle and GNG in liver (Increase glucose availability)  Stimulate lipolysis in adipose tissue (TAG → FFA and glycerol) ↑ ATP production (FFA beta-oxidation), glycerol enters GNG pathway  ↑ basal metabolic rate FIGHT OR FLIGHT RESPONSE