Introduction to Endocrine Physiology PDF

Introduction to Endocrine Physiology Dr. Sovan Bagchi Professor of Physiology * www.gmu.ac.ae COLLEGE OF MEDICINE  Learning Objectives Class...

Introduction to Endocrine Physiology Dr. Sovan Bagchi Professor of Physiology * www.gmu.ac.ae COLLEGE OF MEDICINE  Learning Objectives Classify hormones based on the structure Describe synthesis, secretion, and transport of hormones Explain the mechanism of action of hormones  Introduction to Endocrine Physiology 1. Nervous control 2. Hormonal control Hormone controls metabolic functions of the body - secreted by group or single cell Examples Rate of chemical reactions Transport of chemical substances Growth & development Water and electrolyte balance Secretion etc.  Nature of hormones Some hormones acts locally called local hormones like acetylcholine (ACh) Some hormones exert their action on all cells of the body called general hormone like growth hormone, Thyroid hormone etc. Some of the hormones acts on specific target tissues Eg. adrenocorticotropic hormone (ACTH) act on adrenal cortex Principle endocrine glands of the body  Chemical structure of hormones 1. Protein & polypeptide hormones: Eg. Anterior and Posterior pituitary hormones, Pancreatic hormones etc. 2. Steroid hormones: having steroid nucleus and derived from cholesterol Eg. Cortisol, Aldosterone, Testosterone, Estrogen etc. 3. Amino acids (tyrosine) derivatives: Eg. T3,T4, Epinephrine, Norepinephrine etc. Synthesis, Storage and secretion of hormones All protein hormones are formed by rough ER as preprohormone -biologically inactive Cleaved into smaller protein called prohormone in ER. Transported to Golgi apparatus and cleavage of another protein part makes prohormone to biologically active hormone In golgi apparatus they are packed as secretary vesicle and stored. Specific signal cause the secretion. Synthesis and storage  Steroid hormones are stored in small quantities on specific signal enzymes act on precursor molecules to synthesize hormones. Thyroid hormone formed as part of large protein Thyroglobulin and stored in follicle of thyroid gland. Norepinephrine and epinephrine are formed and stored in secretary granules secreted by exocytosis Feedback control of hormone secretion Hormone secretion are generally regulated by internal control mechanism. This is controlled by negative feed back mechanism Negative feedback effect to prevent oversecretion of the hormone or overactivity at the target tissue. Negative feed back mechanism + Hormone Endocrine On target Gland cell Hormone - Some other regulation Surges: Luteinizing hormone (LH) secretion occurs as a result of stimulatory effect of estrogen before ovulation - positive feedback mechanism LH cause more secretion estrogen which cause more secretion of LH. Positive feed back mechanism + Hormone Endocrine On target Gland cell Hormone +  Cyclical variations This is superimposed on positive or negative feed back control. Periodic variation in hormone release. They are influenced by seasonal changes, sleep, daily cycle etc. Eg. GH secretion is more during early stage of sleep and becomes less during late phase.  Transport Peptide hormones generally dissolved in plasma and transported from their site of synthesis to target issues. Steroid and thyroid hormones circulate in blood mainly bound to plasma proteins. 99% of Thyroid hormone bound to plasma protein - Bound hormones are physiologically inactive as they cannot diffuse across the capillaries – reservoirs.  Clearance of Hormones Two factors can increase or decrease the concentration of a hormone in the blood. 1. The rate of hormone secretion into the blood. 2. The rate of removal of the hormone from the blood, which is called the metabolic clearance rate.  Mechanisms of Action of Hormones Generally, they act through specific receptor and this receptor-hormone complex leads to cascade action. Membrane receptors: Peptide hormone receptor. Cytoplasmic receptor: steroid hormone Nucleus receptor: T3 and T4 The number of receptors in a target cell usually does not remain constant. Up regulation and down regulation is common in hormonal action  Intracellular Signaling Hormone exert their action on target tissues by activating its receptor This receptor brings hormone action. Ion Channel-Linked Receptors - Change membrane permeability Hormone combines with receptor and cause conformational change By this change it cause opening and closing of channel of some ions. Eg. ACh cause opening of Na channels. G Protein-Linked Hormone Receptors Enzyme-Linked Hormone Receptors Janus kinase 2  Activation of intracellular enzymes Hormone binding to a membrane receptor activates enzymes inside the cell membrane. Activates adenylyl cyclase this leads to formation of cAMP cAMP act as second messenger and exerts intracellular change. cGMP also act in similar fashion  By activating gene Some steroid hormone and thyroid hormone binds to receptor inside the cells. This receptor hormone complex activates specific portion of DNA of cell nucleus. This initiates transcription of specific gene and newly protein produced.  Second messenger Cyclic AMP Hormone binds to receptor on the surface of the cell. The portion of the membrane that projected toward interior activates enzymes adenylyl cyclase. This adenylyl cyclase converts ATP to cAMP  cAMP activates cascade of enzyme. This cascading mechanism initiates biological action like secretion, contraction and relaxation of muscle etc. Eg. cAMP cause LH, ACTH, FSH, Glucagon, Calcitonin, Catecholamines etc. Calcium-Calmodulin second messenger system Changes in membrane potential that open Ca channels or Hormone binding to its receptor that cause opening of Ca channels Ca after entering into the cell binds with calmodulin Calmodulin has four binding sites and when it bind with four Ca++ conformational change occurs. This activated calmodulin now activate several other enzymes and cause different intracellular reactions.  Phospholipid second messenger system Some hormone activate transmembrane receptors. This leads to phospholipase C activation. Phospholipase C cause splitting off phosphatidylinositol biphosphate (PIP2). The break down products are inositol triphosphate (IP3) and diacylglycerol (DAG).  IP3 cause mobilization of Ca and Ca exert their action to bring biological action. DAG activates protein kinase C and cause cell division and proliferation. This action is enhanced by Ca that have been released by IP3 Eg. Angiotensin II, TRH, Oxytocin etc.  Learning Resources Textbook: John E. Hall and Michael E. Hall. Textbook of Medical Physiology. 14th ed. Elsevier. 2021. ISBN: 978-0-323- 59712-8. Chapter: 75 Page no. 915-927 Power-point presentation in the moodle January 18, 2025 www.gmu.ac.ae COLLEGE OF PHARMACY  Thank You January 18, 2025 www.gmu.ac.ae COLLEGE OF PHARMACY