Adrenal Glands and Pancreas PDF

The adrenal glands and the pancreas Unit: AGEP Endocrinology Unit code: VETS10018 Dr Nobue Itasaki Learning Outcomes Describe and explain the hypothalamic-pituitary-adrenal axis. Contrast the functions of the adrenal medulla and adrenal cortex. Explain the synthesis, secretion, and mechan...

The adrenal glands and the pancreas Unit: AGEP Endocrinology Unit code: VETS10018 Dr Nobue Itasaki Learning Outcomes Describe and explain the hypothalamic-pituitary-adrenal axis. Contrast the functions of the adrenal medulla and adrenal cortex. Explain the synthesis, secretion, and mechanism of action of: Norepinephrine and epinephrine Aldosterone Cortisol and cortisone Insulin Glucagon  Recap from the last lecture Important concepts Systemic regulation of cells can occur in two ways: Endocrine system Nervous system The endocrine system communicates with cells by chemical messengers, hormones. Hormones circulate in the blood and diffuse through interstitial tissues. Only cells with the receptor for the hormone are influenced by it. The actions of hormones tend to be slower in taking effect but have a longer duration than the nervous system.  Recap from the last The main organs of the endocrine system lecture Adrenal glands - Paired & located close to kidneys. Pituitary gland - Consisting of the cortex and - Appendage of the brain. medulla Kidney - Produces several - Cortex produces - produce renin, erythropoietin etc hormones directly mineralocorticoids, glucocorticoids influencing other & sex steroids. Ovary endocrine glands (FSH, LH, - The medulla produces adrenaline - Produce the sex ACTH, TSH, prolactin, STH and noradrenaline hormones oestrogen (GH)). and progesterone. Parathyroid gland Testis - Usually 4 glands near thyroid. - Produce the sex - Secrete parathyroid hormone hormones oestrogen - Regulates calcium metabolism. and testosterone. Thyroid gland - Located over trachea Pancreas - Produces hormones. - Produces insulin and concerned with glucagon. Also secretes metabolism and growth digestive enzymes by T4 & T3 and calcitonin exocrine Adrenal glands  Adrenal glands Paired, located craniomedially to the corresponding kidney. Lie against the roof of the abdomen by the thoracolumbar region. The glands are retroperitoneal, meaning they lie behind the peritoneum. https://www.wellnessvet.com.hk/services/internal-medicine/addison-disease-hypoadrenoco Learning Outcomes Describe and explain the hypothalamic-pituitary- adrenal axis. Contrast the functions of the adrenal medulla and adrenal cortex. Explain the synthesis, secretion, and mechanism of action of: Norepinephrine and epinephrine Aldosterone Cortisol and cortisone Insulin Glucagon Hypothalamic – pituitary- adrenal (HPA) axis Corticotropin-releasing hormone (CRH) (= ACTH-RH) High levels of is secreted by the glucocorticoids hypothalamus negatively feedback to the It acts on the anterior lobe pituitary gland of the pituitary gland. and In response to this, ACTH is hypothalamus, secreted. and suppress further secretion of ACTH-RH and ACTH works on the adrenal ACTH cortex and stimulates the secretion of hormones (mainly glucocorticoids) that work on target organs Major Hypothalamic hormones functioning on anterior pituitary Hormone Effect of anterior Chemical pituitary structure Corticotropin Causes release of ACTH Peptide releasing hormone (CRH) Thyrotropin releasing Stimulates secretion of Peptide Hypothalamus hormone (TRH) TSH and prolactin Growth hormone Causes release of growth Peptide releasing hormone hormone (GHRH) Somatostatin or Inhibits the release of Peptide Growth hormone growth hormone inhibitory hormone Pituita (GHIH) ry gland Gonadotropin Causes release of LH and Peptide releasing hormone FSH (GnRH) anterior posterior Prolactin releasing Causes release of ? Corticotropin = Hormones secreted FSH = follicle stimulating hormone LH = Lutenising hormone from the anteiro ACTH = Adrenocorticotropic hormone TSH = Thyroid stimulating hormone pituitary gland GH = growth hormone (or somatotrophin All are peptides Mineral corticoids and sex steroids would also be secreted in response to ACTH, but other mechanisms also induce the Histology of the adrenals Cap = capsule C = cortex G = zona glomerulosa (mineralocorticoi ds) F = zona fasciculata (glucocorticoids) R = zona reticularis (androgens) Learning Outcomes Describe and explain the hypothalamic-pituitary-adrenal axis. Contrast the functions of the adrenal medulla and adrenal cortex. Explain the synthesis, secretion, and mechanism of action of: Norepinephrine and epinephrine Aldosterone Cortisol and cortisone Insulin Glucagon  Adrenal glands The cortex and medulla are independent tissues, with different origin Young et al. Wheater's Functional Histology 6th Ed. Elsevier Cortex Medulla produces; produces; Mineralocorticoi Norepinephrine ds (noradrenaline) Glucocorticoids Epinephrine (adrenaline) Sex steroids  Adrenal cortex and medulla Adrenal cortex Adrenal medulla Who stimulates ACTH, which is secreted Sympathetic neurons the hormone from the anterior pituitary secretion? gland What hormones Mineralocorticoids Norepinephrine are secreted? (incl. Aldosterone) (Noradrenaline) Glucocorticoids (incl. Epinephrine (Adrenaline) Cortisol, corticosterone) Sex steroids (Androgens and Oestrogens) What is the Regulate water/salt “fight-or-flight” response effect of the balance hormones? Control metabolism and Equivalent to post- inflammation synaptic Sexual and reproductive sympathetic neurons function (respectively) Adrenal cortex  Adrenal cortex Adrenal cortex ACTHAdrenal medulla = Adrenocorticotropic hormone ACTH is also called Corticotropin Who stimulates ACTH, which is secreted Sympathetic neurons the hormone from the anterior pituitary The release of ACTH is secretion? gland regulated by Corticotropin- releasing hormone (CTR) (= What hormones Mineralocorticoids Norepinephrine ACTH-RH) secreted by the are secreted? (incl. Aldosterone) (Noradrenaline) thalamus. These are all steroid hormones Glucocorticoids (incl. Epinephrine (Adrenaline) (formed from cholesterol) Cortisol, corticosterone) => called Corticosteroids Sex steroids (Androgens and Oestrogens) What is the Regulate water/salt “fight-or-flight” response When we say ‘steroid effect of the balance tablet was prescribed’, it hormones? Control metabolism and Equivalent usually to post- means inflammation synaptic glucocorticoids for their Sexual and reproductive anti-inflammatory sympathetic effect. neurons Androgens and Oestrogens function (respectively) are also produced by the testis and ovary  Adrenal cortex The cortex secretes corticosteroids. These hormones are synthesised from cholesterol. Thus, have similar chemical structures but distinct functions. Three main types of cortical hormones are produced: 1. Mineralocorticoids – the main one is Aldosterone. Regulate electrolytes of ECF, particularly Na+ & K+. 2. Glucocorticoids – the main ones are Cortisol and Corticosterone. Control metabolism and inflammation, thus combating stress Learning Outcomes Describe and explain the hypothalamic-pituitary-adrenal axis. Contrast the functions of the adrenal medulla and adrenal cortex. Explain the synthesis, secretion, and mechanism of action of: Norepinephrine and epinephrine Aldosterone Cortisol and cortisone Insulin Glucagon  1. Mineralocorticoid - Aldosterone Promote to reabsorb Na+ and H2O, excrete K+ => increase ECF and blood pressure Synthesis and secretion of aldosterone is primarily regulated by: The renin-angiotensin II – Extracellular [K+] aldosterone system (RAAS) [K+] acts directly on Renin is an enzyme produced in aldosterone-producing cells. the kidneys, stimulated by BP↓ and sympathetic nervous The ↑[K+] depolarises cell system stimulation to kidneys. membrane of aldosterone producing cells, opening Ca2+ Angiotensin II formed by renin voltage-gated channels, ↑ stimulates release of [Ca2+] stimulating aldosterone aldosterone from the adrenal synthesis. cortex.  Slide from Blood Pressure lectur Kidney's response to low blood pressure ↓ mean arterial pressure angiotensinogen ↑ renin secretion from kidneys angiotensin I Angiotensin converting enzyme (ACE) in vasoconstricti angiotensin II lungs ↑ mean arterial on pressure ↑ Na+ and water ↑ aldosterone reabsorption from from adrenal kidney tubules cortex  1. Mineralocorticoid - Aldosterone Aldosterone promotes reabsorption of Na+ and excretion of K+ in: Distal tubules and collecting ducts of kidneys Salivary and sweat glands, large intestine. Reabsorption of Na+ is accompanied by water reabsorption Resulting in increased volume of the extracellular fluid and increased blood pressure.  2. Glucocorticoids The main glucocorticoids are cortisol (also called hydrocortisone) and corticosterone Transported in blood tightly bound to corticosteroid- binding globulin and albumin. Secretion is stimulated by ACTH and regulated by the negative feedback system involving the hypothalamus, pituitary and adrenal cortex. Glucocorticoids are lipid soluble. They diffuse through cell membranes, bind to receptors in the cytoplasm, translocate into the nucleus and regulate the transcription of specific genes. All nucleated cells in the body have glucocorticoid receptors  2. Glucocorticoids - function Regulate metabolism of carbohydrate, protein and fat Also have anti-inflammatory activity Glucocorticoids affect many processes: Glucose metabolism – stimulate hepatic gluconeogenesis and glycogenesis (glycogen storage) Protein metabolism – stimulate protein break-down in skeletal muscles. In liver, (re catabolic effect) Lipid metabolism – mobilise fatty acids from lipid tissues, store triglycerides in the liver Combat stress – mainly to increase blood glucose level Anti-inflammation – to reduce or reverse inflammatory and allergic responses Modulate the effect of other hormones – e.g. insulin, glucagon, growth hormone, angiotensin II, catecholamines DNA synthesis – inhibit DNA synthesis initially in many tissues to reduce growth and facilitate survival  2. Glucocorticoids - function Glucocorticoids ↑ blood glucose Barker et al., 2023 Learning Outcomes Describe and explain the hypothalamic-pituitary-adrenal axis. Contrast the functions of the adrenal medulla and adrenal cortex. Explain the synthesis, secretion, and mechanism of action of: Norepinephrine and epinephrine Aldosterone Cortisol and cortisone Insulin Glucagon Adrenal medulla  Adrenal medulla The core part of the adrenal gland. Originally equivalent to the post-ganglionic (post-synaptic) sympathetic neural cells. Produces norepinephrine, epinephrine and dopamine (catecholamines) Secretion is stimulated by increased activity in preganglionic nerve fibres that innervate cells in the adrenal medulla. The hormone secretion is an integrated part of the sympathetic nervous system. The hormones stimulate “fight-or-flight” response Catecholamines: A group of chemical hormones including norepinephrine, epinephrine, dopamine Adrenal medulla E, NE E, NE https://www.youtube.com/watch?v=ybd6MuSFe8A Secretion of catecholamines from the adrenal medulla The preganglionic nerve fibres release Ach, depolarising the cell membrane, generating an AP and influx of Ca2+, and exocytosis of vesicles containing catecholamines. Adrenal medulla Catecholamines are synthesised from the amino acid tyrosine. Adrenal secretion: Epinephrine > Norepinephrine. Catecholamines circulate freely in the blood.  Receptors and neurotransmitters (Review) AC h N Somati c AC h N NE α or β Sympath AC h N NE, etic E AC h N AC h M AC h N AC h M Parasympat hetic N = nicotinic receptor (Nicotine works as an agonist) M = muscarinic receptor (Muscarine works as an agonist) a,b = adrenergic receptor  Norepinephrine and epinephrine bind to both α and β Adrenergic receptors receptors. α receptors have highest affinity for norepinephrine. β receptors have highest affinity for epinephrine. Receptor Physiological effect s α1 Constrict vascular smooth m. (vasoconstriction) Contract radial m. of eye Contract vas deferens smooth m. α2 Inhibit norepinephrine release from presynaptic neuron Centrally induce sedation Centrally mediate pain modification β1 Increase cardiac output Increase renin release from kidney β2 Relax bronchial smooth m. Relax vascular smooth m. (vasodilation) Reduction of mast cell degranulation and histamine release β3 Increase adipose tissue lipolysis Learning Outcomes Describe and explain the hypothalamic-pituitary-adrenal axis. Contrast the functions of the adrenal medulla and adrenal cortex. Explain the synthesis, secretion, and mechanism of action of: Norepinephrine and epinephrine Aldosterone Cortisol and cortisone Insulin Glucagon The pancreas Insulin Glucagon Pancreas The pancreas has both exocrine and endocrine components. The exocrine component produces digestive juice, which is discharged into the duodenum via one or two Young et al. Wheater's Functional Histology 6th Ed. Elsevier ducts. The juice contains enzymes which break down proteins, carbohydrates and fats. The endocrine portion consists of islets of Langerhans that are the source of insulin, glucagon, and somatostatin + gastrin. Glucagon alpha cell Insulin beta cell Somatostatin, gastrin delta cell The pancreas – endocrine part The endocrine part of the pancreas produces mainly two hormones involved in metabolism: Insulin Glucagon The main role is to regulate the blood glucose level Four different types of endocrine cells have been identified in the islets of Langerhans: 1. Alpha – produce glucagon, regulate metabolism of carbohydrate, protein and fats 2. Beta – produce insulin, regulate metabolism of carbohydrate, protein and fats 3. Delta – produce somatostatin, paracrine function in the regulation of insulin and glucagon 4. (PP – produce pancreatic polypeptide, concerned with GIT function) The pancreas transports the hormones to the portal vein, the portal vein conducts blood from the GIT  The pancreas - Insulin Insulin is the body’s most important anabolic signal. Insulin secretion increases after meals in response to the rise in glucose and amino acids in the blood. Insulin is a peptide hormone. β cells in the islets of Langerhans synthesise proinsulin which is converted to active insulin after removal of C-peptide prior to secretion. ism: The process of breaking down complex molecules into simpler ones, releasing energy in the process. (e.g. glycogen sm: The process of building complex molecules from simpler ones, consuming energy in the process. The pancreas - Insulin Insulin secretion is stimulated by several factors. The main factor is increase of glucose concentration in the plasma. Amino acids, glucagon polypeptide 1, gastrin inhibitory polypeptide also stimulate release. Glucose is transported into the β-cells by a glucose transporter (GLUT) and the β- cell glucose concentration mediates secretion of insulin. Increased activity of the parasympathetic nerve fibres that innervate the islets of Langerhans also stimulates insulin secretion. Norepinephrine from the sympathetic nervous system and epinephrine from the adrenal medulla inhibit insulin secretion.  Link this to teaching on metabolism in GIT The pancreas - Insulin Insulin has important effects on the metabolism of carbohydrates, proteins, and fats: Cellular glucose uptake and glycogen synthesis are stimulated Cellular amino acid uptake and protein synthesis are stimulated Enzymes involved in the metabolism of glucose, amino acids, and lipids are activated The net effect of the actions of insulin is to: o lower blood concentrations of glucose, fatty acids and amino acid o promote intracellular storage of glycogen, triglycerides, and prote  The pancreas - Glucagon Glucagon is produced in the α-cells. The effects of glucagon on metabolism tend to be the opposite to insulin. The primary target organ for glucagon is the liver, by stimulating mobilisation of glucose from glycogen (catabolism) and gluconeogenesis. Glucagon secretion is stimulated by declining glucose levels in the blood and inhibited by an increase. ism: The process of breaking down complex molecules into simpler ones, releasing energy in the process. (e.g. glycogen sm: The process of building complex molecules from simpler ones, consuming energy in the process. The pancreas - Glucagon Glucagon is stimulated by elevated concentrations of amino acids just like insulin. Why? Well, what would happen if an animal ate a meal high in protein and low in carbohydrates and only insulin responded to elevated amino acids in the plasma? The pancreas - Glucagon Sympathetic nerve fibre activity increase glucagon secretion and increased epinephrine – the opposite to insulin. Insulin and glucagon are also paracrine hormones within the islets of Langerhans to one another. Insulin inhibits the release of glucagon and glucagon inhibits the secretion of insulin. The major functions of glucagon are: Decreasing glycogen synthesis Increasing glycogen degradation Enhancing glucose production Mobilises fatty acids from fat tissue References Sjaastad et al (2016). Physiology of domestic animals. (3rd ed.). Oslo, Norway: Scandinavian Veterinary Press. Guyton & Hall (2006). Textbook of medical physiology (11th ed.). Philadelphia: Saunders/Elsevier. Klein (2019) Cunningham’s textbook of veterinary physiology (6th ed.). St Louis, Missouri: Saunders/Elsevier. Barker, H.L., Morrison, D., Llano, A. et al. Practical Guide to Glucocorticoid Induced Hyperglycaemia and Diabetes. Diabetes Ther 14, 937–945 (2023). doi.org/10.1007/s13300-023-01393-6