Introduction to Endocrinology - Warwick Medical School

Introduction to Endocrinology Dr Anthony Lyons Email: [email protected] MB ChB Phase I Block 1 Health, Metabolism and Homeostasis Learning Outcomes 1. Define the terms endocrinology, endocrine, hormone, exocrine, paracrine and autocrine. 2. List the main endocrine organs. 3. List the...

Introduction to Endocrinology Dr Anthony Lyons Email: [email protected] MB ChB Phase I Block 1 Health, Metabolism and Homeostasis Learning Outcomes 1. Define the terms endocrinology, endocrine, hormone, exocrine, paracrine and autocrine. 2. List the main endocrine organs. 3. List the main hormones and describe their physiological function, site of action and signalling mechanisms. 4. Describe the key characteristics (synthesis, transport and signalling mechanisms) of the main molecular types of hormones. 5. Describe the principles of positive and negative feedback. 6. Describe the basis of endocrine disease. 7. Compare primary and secondary endocrine dysfunction.  What is Endocrinology? Endocrinology - “the branch of physiology and medicine concerned with endocrine glands and hormones” The science of the system. structure and function An ‘Endocrinologist’ is a of the endocrine physician who treats glands, and the disorders of the diagnosis and endocrine system. treatment of disorders of the endocrine  What is an Endocrine gland? A hormone is molecule that is released in one part of the body, but regulates the activity of cells in other parts of the body. Endocrine gland: A gland that produces and secretes hormones into the bloodstream, through which they travel to affect distant targets. Exocrine gland: A gland that secretes its products into ducts opening onto an epithelium. Paracrine: of, relating to, promoted by, or being a substance secreted by a cell and acting on adjacent cells. Autocrine: of, relating to, promoted by, or being a substance secreted by Manu, Mitra. (2018). Pancreatic Cancer and its Treatment. Journal of Gastrointestinal and Hepatic a cell and acting on surface receptors Surgery. 1. 10.36959/879/373. of the same cell.  Tan, M. (2016). Cell and molecular biology for diagnostic and therapeutic technology. Journal of Physics: Conference Series. 694. 012001. 10.1088/1742-6596/694/1/012001. Endocrine: relating to or denoting glands which secrete hormones or other products directly into the blood. Paracrine: of, relating to, promoted by, or being a substance secreted by a cell and acting on adjacent cells. Autocrine: of, relating to, promoted by, or being a substance secreted by a cell and acting on What is the Endocrine System? The endocrine system integrates organ function via chemicals that are secreted from endocrine tissues or “glands” into the extracellular fluid. These chemicals, called hormones, are then carried through the blood to distant target tissues where they are recognized by specific high- affinity receptors. Receptor molecules allow the target cell to recognize a unique hormonal signal from among the numerous chemicals that are carried through the blood and Marieb, Elaine N., and Suzanne M. Keller. Essentials of Human Anatomy & Physiology, Global Edition, Pearson Specificity and selectivity of hormone receptors Chapter 42 - Harpers Illustrated Biochemistry 29th Edition (LANGE Basic Science)  Endocrine Organs What is their function? Gland Hormone Produced Effects Hypothalamus Antidiuretic hormone Acts on the kidney to regulate fluid balance Pituitary Many hormones, e.g. Growth and regulates oxytocin other glands Thyroid Thyroxine Metabolism Pancreas Insulin & Glucagon Blood sugar Adrenal Epinephrine Heart rate & blood pressure Testes Testosterone Sperm & male characteristics Ovaries Estrogen & progesterone Eggs & female characteristics Textbook of medical physiology / Arthur C. Guyton, John E. Hall  Hormones Hormones play a critical role in the regulation of physiological processes because of the target cell responses they regulate… BUT WHAT ARE HORMONES? Hormones are chemical substances that are secreted by cells into extracellular fluids and regulate a variety of activities throughout the body. There are three general classes of hormones:  Proteins and polypeptides, including hormones secreted by the anterior and posterior pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid hormone), and many others.  Steroids secreted by the adrenal cortex (cortisol and aldosterone), the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone).  Amines - derivatives of the amino acid tyrosine, secreted by the thyroid (thyroxine and triiodothyronine) and the adrenal medullae (epinephrine and norepinephrine). OpenStax College - Anatomy & Physiology, Connexions Web site. Hormone Classes Hormones can be classified according to: chemical composition, solubility properties, location of receptors, and nature of the signal used to mediate hormonal action within the cell. Chapter 42 - Harpers Illustrated Biochemistry 29th Edition (LANGE Basic Science) Marieb, Elaine N., and Suzanne M. Keller. Essentials of Human Anatomy & Physiology, Global Edition, Pearson Education Stimuli for Control of Hormone Release a) The most common stimulus is a hormonal stimulus, in which endocrine organs are prodded into action by other hormones. b) Changing blood levels of certain ions and nutrients may also stimulate hormone release. Such stimuli are referred to as humoral stimuli c) In isolated cases, nerve fibers stimulate hormone release, and the endocrine cells are said to respond to neural stimuli. Marieb, Elaine N., and Suzanne M. Keller. Essentials of Human Anatomy & Physiology, Global Edition, Pearson Education  Pathways of Hormone Action The response triggered by a hormone depends not only on the hormone, but also on the receptor present on the target cell…. HOW ARE CELLULAR RESPONSES TRIGGERED BY HORMONES? Pathways Involving Intracellular Hormone Receptors A steroid hormone directly initiates the production of proteins within a target cell. Steroid hormones easily diffuse through the cell membrane. The hormone binds to its receptor in the cytosol, forming a receptor–hormone complex. The receptor–hormone complex then enters the nucleus and binds to the target gene on the DNA. Transcription of the gene creates a messenger RNA that is translated into the desired protein within the cytoplasm. OpenStax College - Anatomy & Physiology, Connexions Web site. Steroid hormone and thyroid hormone mechanism Steroid (or thyroid) hormone diffuses across the cell membrane and binds to its receptor. The hormone-receptor complex enters the nucleus and dimerizes (step 2). The hormone-receptor dimers are transcription factors that bind to steroid-responsive elements (SREs) of DNA (step 3) and initiate DNA transcription (step 4). New messenger RNA is produced, leaves the nucleus, and is translated to synthesize new proteins (step 5). The new proteins that are synthesized have specific physiologic actions. For example, aldosterone induces the synthesis of Na+ channels in the renal principal cells. Pathways of Hormone Action Pathways Involving Cell Membrane Hormone Receptors Water-soluble hormones cannot diffuse through the cell membrane. These hormones must bind to a surface cell-membrane receptor. The receptor then initiates a cell- signaling pathway within the cell involving G proteins, adenylyl cyclase, the secondary messenger cyclic AMP (cAMP), and protein kinases. In the final step, these protein kinases phosphorylate proteins in the cytoplasm. This activates proteins in the cell that carry out the changes specified by the hormone. OpenStax College - Anatomy & Physiology, Connexions Web site. Hormone Action Endocrine regulation occurs through feedback control The hormone-secreting cell functions as a “sensor” that continually monitors the circulating concentration of some regulated variable. When the endocrine gland senses that too much (or too little) of the regulated variable is circulating in blood, it responds by decreasing (or increasing) the rate of hormone secretion. This response in turn affects the metabolic or secretory behavior of the target tissue. → may either directly feed back to the sensing cell or stimulate some other cell that eventually signals the sensor regarding whether the altered function of the endocrine gland has been effective. Fig 47.2 Medical Physiology, 3e Walter F. Boron, Emile L.  Regulation of Hormone Secretion 1. Negative feedback 2. Positive feedback is the most commonly applied principle for is rare. regulating hormone secretion. is explosive and self-reinforcing. is self-limiting. A hormone has biologic actions that, directly A hormone has biologic actions that, directly or or indirectly, cause more secretion of the indirectly, inhibit further secretion of the hormone. hormone. For example, the surge of luteinizing For example, parathyroid hormone is secreted hormone (LH) that occurs just before by the chief cells of the parathyroid gland in response to a decrease in serum Ca2+ ovulation is a result of positive feedback of concentration. estrogen on the anterior pituitary. →parathyroid hormone’s actions on bone, kidney, →LH then acts on the ovaries and causes more and intestine all act in concert to increase the secretion of estrogen. serum Ca2+ concentration. →The increased serum Ca2+ concentration then decreases further parathyroid hormone secretion. Adrenocorticotropic Hormone The adrenocorticotropic hormone (ACTH), also called corticotropin, stimulates the adrenal cortex to secrete corticosteroid hormones such as cortisol. The release of ACTH is regulated by the corticotropin-releasing hormone (CRH) from the hypothalamus in response to normal physiologic rhythms. Fig 47.2 Medical Physiology, 3e Walter F. Boron, Emile L.  Hormones of the Adrenal Cortex Cortex and medulla originate from 2 distinct embryological tissues and produce different types of hormones / neuro-hormones. The adrenal cortex produces three major groups of steroid hormones, which are collectively called corticosteroids — 1. mineralocorticoids, 2. glucocorticoids, and 3. sex hormones. OpenStax College - Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/ Hormones of the Zona Glomerulosa Called mineralocorticoids because of their effect on body minerals, especially Na+ and K+. These hormones are essential for fluid and electrolyte balance. Aldosterone is the major mineralocorticoid. It is important in the regulation of the concentration of sodium and potassium ions in urine, sweat, and saliva. For example, it is released in response to elevated blood K+, low blood Na+, low blood pressure, or low blood volume. In response, aldosterone increases the excretion of K+ and the retention of Na+, which in turn increases blood volume and blood pressure. Its secretion is prompted when CRH from the Fig 47.2 Medical Physiology, 3e Walter F. Boron, Emile L. Boulpaep hypothalamus triggers ACTH release from the anterior pituitary. Hormones of the Zona Fasciculata The cells of the zona fasciculata produce hormones called glucocorticoids because of their role in glucose metabolism. The most important of these is cortisol, some of which the liver converts to cortisone. In response to long-term stressors, the hypothalamus secretes CRH, which in turn triggers the release of ACTH by the anterior pituitary. ACTH triggers the release of the glucocorticoids. Their overall effect is to inhibit tissue building while stimulating the breakdown of stored nutrients to maintain adequate fuel supplies. Fig 47.2 Medical Physiology, 3e Walter F. Boron, Emile L. Boulpaep Synthesis and Secretion of ACTH When ACTH is secreted by the anterior pituitary gland, several other hormones that have similar chemical structures are secreted simultaneously. The reason for this is that the gene that is transcribed to form the RNA molecule that causes ACTH synthesis initially causes the formation of a considerably larger protein, a preprohormone called proopiomelanocortin (POMC) →precursor of ACTH as well as several other peptides, including: melanocyte stimulating hormone (MSH), β-lipotropin, β-endorphin, and a few others. Harpers Illustrated Biochemistry 29th Edition (LANGE Basic Science) Metabolic Actions of Cortisol Glucocorticoids increase gluconeogenesis by the following mechanisms: 1. They increase protein catabolism in muscle and decrease protein synthesis, thereby providing more amino acids to the liver for gluconeogenesis. 2. They decrease glucose utilization and insulin sensitivity of adipose tissue. 3. They increase lipolysis, which provides more glycerol to the liver for gluconeogenesis. Textbook of medical physiology / Arthur C. Guyton, John E. Hall Effects of glucocorticoids Anti-Inflammatory Actions of Glucocorticoids Cortisol will not only block inflammation from occurring, but it will also reduce inflammation once it has begun. The mechanisms by which this occurs are as follows: 1. Stabilisation of lysosomal membranes – this makes it much more difficult for membranes of lysosomes to rupture, and thus the inflammatory proteins often released in the first stages of inflammation are much less likely to be released. 2. Decreased capillary permeability – this is probably secondary to the first effect. 3. Decreased migration and activity of white blood cells – this is a result of reduced release of inflammatory proteins. 4. General immune system suppression – especially that of T cells. This reduces inflammation, due to the inflammatory actions of T cells on affected areas. 5. Reduction of fever – this is mainly a result of reduced secretion of IL-1 from white blood cells. The reduced temperature will also reduce the amount of vasodilation, and thus reduce oedema.  How can endocrine disorders arise? Abnormalities in a hormone’s effective plasma concentration can arise from a variety of factors. Endocrine disorders most commonly result from abnormal plasma concentrations of a hormone caused by inappropriate rates of secretion; -that is, too little hormone secreted (hyposecretion) -or too much hormone secreted (hypersecretion). Occasionally, endocrine dysfunction arises because target-cell responsiveness to the hormone is abnormally low, even though plasma concentration of the hormone Clinical Case A 36-year-old woman presents to her gynaecologist with complaints of amenorrhea and hirsutism. She has also noticed an increase in her weight (especially in the trunk region) and easy fatigability. She denies any medical problems. Her periods were always normal until 6 months ago, and her hirsutism has been gradual in onset. On examination, she has a very rounded hirsute face with centripetal obesity. Her blood pressure is elevated, as is her weight compared with previous visits. On abdominal examination, she is noted to have striae and a male-like distribution of hair on the lower abdomen. The patient then undergoes studies that demonstrate increased cortisol production and failure to Wide purple striae on the abdom suppress cortisol secretion normally when inal wall due to Cushing’s syndro me dexamethasone is administered. She is diagnosed with Cushing syndrome. Disorders Involving the Adrenal Glands Cushing’s disease is a disorder characterized by high blood glucose levels and the accumulation of lipid deposits on the face and neck. It is caused by hypersecretion of cortisol. The most common source of Cushing’s disease is a pituitary tumor that secretes cortisol or ACTH in abnormally high amounts. A person with Cushing’s syndrome Other common signs of Cushing’s before (left) and after disease include the development of a (right) subtotal adrenalectomy moon-shaped face, a buffalo hump on Textbook of medical physiology / Arthur C. Guyton, the back of the neck, rapid weight gain, John E. Hall and hair loss. Cushing syndrome Chronically elevated glucose levels are also associated with an elevated risk of developing type 2 diabetes. In addition to hyperglycemia, chronically elevated glucocorticoids compromise immunity, resistance to infection, and memory, and can result in rapid weight gain and hair loss.  Disorders Involving the Adrenal Glands Hyposecretion of corticosteroids can result in Addison’s disease, a rare disorder that causes low blood glucose levels and low blood sodium levels. The signs and symptoms of Addison’s disease are vague, making diagnosis difficult. They may include general weakness, abdominal pain, weight loss, nausea, vomiting, sweating, hyperpigmentation and cravings for salty food. Addison's disease - The Lancet - Case Presentation The Lancet Vol 365 June 11, 2005 Thank you! Email: [email protected] Adrenal Insufficiency & Addison’s Disease Cushing’s Syndrome