ENDOCRINE OVERVIEW Dr. Amel Eassawi OBJECTIVES The student should be able to: Describe the basic physiologic functions of the endocrine system and contrast these functions with the basic functions of the nervous systems. Define hormone, neurohormone, target cell and receptor. Define endocrine, paracrine, autocrine, and intracrine. Describing the chemical nature of hormones. Explain hormone synthesis, storage, and mechanism of secretion for peptide/ protein, amine and steroid hormones. Understanding the different mechanisms of hormonal action and the concept of second messenger system. 2 INTRODUCATION All body systems contribute to maintain homeostasis but the two major regulatory systems in the body are: 1. Nervous system: Coordinates rapid and precise response and adjusts the bodys interaction to external environment. 2. Endocrine system: Controls activities needing time rather than speed. Regulates, coordinates and integrates cellular functions at a distance to maintains homeostasis. The nervous system and the endocrine system act together to coordinate functions of all other body systems. 3 ENDOCRINE SYSTEM General Principles: The Endocrine system consist of ductless glands present throughout the body. These glands are not connected with each other anatomically, but functionally make a system. Their function is carried out by hormones secreted by each gland into the blood. Hormones act on distant target cells regulating or directing a particular function. Hormones only act on specific target cells due to presence of receptors. Binding of hormones with receptors initiate a chain of intracellular reactions. 4 ENDOCRINE SYSTEM 5 Definitions : Endocrinology is the study of the homeostatic chemical adjustments and other activities accomplished by hormones, which are secreted into the blood by endocrine glands. Hormones: A long distance chemical messengers that is secreted by an endocrine gland into the blood in response to appropriate signal. The hormone transport to its target cells to exert its effect. Neurohormones: Hormones secreted by neurons. Example: Anti Diuretic Hormone (ADH) and Oxytocin. Target cell: Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells. Receptors: a structure on the surface of a cell or inside a cell that selectively receives and binds a specific substance. A cell is a target because is has a specific receptor for the hormone. ENDOCRINE SYSTEM Functions of the Endocrine System: Regulates metabolism, and water and electrolyte balance. Helps body cope with stressful situations. Promotes sequential growth and development. Controls reproduction. Regulates red blood cell production. Controls and integrates circulation and digestion and absorption of food. 6 7 Endocrine Glands and Tissues 8 ENDOCRINE GLANDS AND THEIR HORMONES 9 Releasing hormones/ factors: Secreted by hypothalamus affects the anterior pituitary gland to produce tropic hormones. Tropic hormones are GHRH, TRH,CRH,GNRH, PRH, Somatostatin and Dopamine. Tropic hormones: Secreted by anterior Pituitary gland to regulate secretion and production of another hormone by other endocrine gland. Tropic hormones are TSH, ACTH, GH, FSH, LH Example: Thyroid stimulating hormone(TSH) stimulates thyroid gland to secrete thyroid hormones thyroxin(T4) and triiodothyronine(T3)and maintains the structure of thyroid gland. In absence or deficiency of TSH, thyroid gland atrophies and produce low levels of thyroid hormones. 10 (d) Cell-to-Cell Communication 11 CELL-TO-CELL COMMUNICATION Neurotransmitters: Are chemicals secreted by neurons that diffuse across a small gap (synapse) to the target cell. Neurons use electrical signals as well. Paracrine Horomones: Site of synthesis and site of action are close. Hormones act on adjacent cells. Autocrine Horomnes: Site of synthesis and target cell are the same. Intracrine Hormones: Act on the same cell through intracellular receptors. Mostly nuclear receptors. Recurrent / Periodic Glands Appear and disappear according to physiological demand Example Corpus Luteum and Placenta. 12 CLASSIFICATION OF HORMONES Hormones are classified chemically as: 1. Hydrophilic (water soluble) 1. Peptide hormones 2. Amines - Catecholamines - Indoleamines 2. Lipophilic (fat soluble) 1. Steroid hormones 2. Amines -Thyroid hormones 13 CLASSIFICATION OF HORMONES 14 CLASSIFICATION OF HORMONES 1. Peptides hormones: Numerous, having a variable chain of amino acids 100 amino acids protein Examples: Anterior and posterior pituitary gland hormones, Insulin, Glucagon, and Parathyroid hormone. 2. Amines: A. Catecholamine: Derived from amino acid tyrosine, secreted from adrenal medulla. Example: Epinephrine. B. Indoleamine: Derived from amino acid tryptophan, produced from pineal gland. Example: Melatonin. C. Thyroid hormone: Is an iodinated tyrosine derivative, Example: thyroid gland hormones. 3. Steroids: Neutral lipids derived from cholesterol, produced by adrenal cortex, testis and ovaries. Example: Cortisol, Aldosterone, Testosterone, and Estrogen. 15 HORMONE SYNTHESIS A. Peptide hormones: Produced and processed by endoplasmic reticulum and golgi complex. Stored in secretary vesicles and release by exocytosis by special signals. Produce physiological response by binding with membrane receptors of target cells. Act primarily by second messenger system altering the activity of preexisting enzymes. The peptide molecule prepared first is usually a larger precursor called as Preprohormone; It is cleaved to form Prohormone; further cleavage of Prohormone, forms the final mature Hormone. Example: Preproinsulin Proinsulin Insulin This hormone is stored in vesicles of endocrine cells and released on demand 16 HORMONE SYNTHESIS B. Amines hormones: Catecholamine and Indoleamine are similar to peptide hormones. Thyroid Hormones: Thyroid hormones are produced by thyroid gland by a unique pathway. Hormones are transported in the blood binding to globulin, Albumin and Hormones are not usually stored except Thyroxin by combining with Thyroglobulin. C. Steroid hormones: Synthesized from cholesterol: Once formed, they are immediately released into the circulation; they are not stored. Steroid producing organs produce only specific hormone not all hormones due to specific enzymes needed for the steps. They exert their effect by combining intracellular receptors. 17 TRANSPOT AND STORAGE OF HORMONES 18 Hormones are Transported: in combination with: Globulin Albumin 2 3% is in FREE FORM (biologically active) Storage: Peptides, catecholamine are stored in vesicles. Steroids and thyroid hormones are not stored except 1. Thyroxin combining with Thymoglobulin. 2. Insulin: stored in cells of pancreas in complex form with Zinc 3. ADH by combining with; - Neurophysin I - Neurophysin II PropertiesPeptidesCatechol- amines Thyroid Hormone Steroids Synthesis and storage Release from parent cell Transport in blood Half life Location of receptor Response to receptor-ligand binding Amines Polyribosomes -ER as Cytosol/ ATP Ca++ Colloid of follicular cells Mitochondria/ preprohormones/ Chromagranin pendrin (iodide/chloride cytosol Vesicles Vesicles transporter Exocytosis Exocytosis thyroglobulin to megalin endocytosis/ lysosomal diffusion degradation Most are free Loosely bound to TBG, transthyretin, albumin sex hormone or albumin albumin corticosteroid BG Minutes 1-2 minutes T4- 7days, T3- 18 days hours plasma membrane plasma membrane intracellular intracellular protein phosphorylation protein phosphorylation genomic genomic genomic genomic Summary of Chemical Structure, Synthesis, and Transport of Hormones COMPLEXITY OF ENDOCRINE FUNCTION A single endocrine gland produces multiple hormones. Anterior pituitary gland secretes six hormones. A single hormone may be secreted by more than one gland. Somatostatin is secreted by the hypothalamus and the pancreas. A single hormone may produce more than one effect. Vasopressin (ADH) affect water reabsorption by acting on V2 receptor and vasoconstriction of arterioles by acting on V1 receptors. The rate of secretions of some hormones varies over course of time in cyclic pattern. Control of menstrual cycle by sex hormones. 20 COMPLEXITY OF ENDOCRINE FUNCTION A single target cell may be influenced by more than one hormone by activating different enzymes. In liver cells Insulin converts glucose into glycogen and Glucagon converts glycogen into glucose. The same chemical messenger may be hormone or a neurotransmitter e.g. Norepinephrine. Some organs have exclusively endocrine function like anterior pituitary gland while, other organs have both endocrine and non endocrine function. Example Testis produces testosterone and sperms. 21 MECHANISMS OF HORMONE ACTION Response depends on both hormone and target cell: Lipid-soluble hormones bind to receptors inside the target cells to cause formation of new intracellular proteins, which in turn produce the desired effect. Water-soluble hormones bind to receptors on the plasma membrane activating second messenger pathways. This activation alter the activity of preexisting intracellular enzymes to produce the desired effect. 22 Target Cells and Receptors 23 Signaling after Activation of Receptor by Hormone: 1. Ion channel receptors: unlike neurotransmitters, most hormones do not open or close ion channels directly 2. Protein-linked receptors G-proteins 3. Enzyme-linked receptors 4. Intracellular receptors MECHANISMS OF HORMONE ACTION G ProteinLinked Hormone Receptors. Many hormones activate receptors that indirectly regulate the activity of target proteins (e.g., enzymes or ion channels) by coupling with groups of cell membrane proteins called heterotrimeric GTP-binding proteins (G proteins) 24 MECHANISMS OF HORMONE ACTION Second Messenger Systems Include: Adenylate cyclase which catalyzes the conversion of ATP to cyclic AMP; Guanylate cyclase which catalyzes the conversion of GMP to cyclic GMP (cyclic AMP and cyclic GMP are known collectively as cyclic nucleotides); Calcium and calmodulin; phospholipase C which catalyzes phosphoinositide turnover producing inositol phosphates and diacyl glycerol. 25 MECHANISMS OF HORMONE ACTION Adenyl Cyclase Hormone binds to the receptor GDP is released from G protein Activate adenyl cyclase which convert ATP to cAMP cAMP activates tyrosine kinase A Tyrosine kinase A phosphorylate specific protein for physiological action 26 MECHANISMS OF HORMONE ACTION Phospholipase C Hormone binds to the receptor Phospholipase C liberates diacylglycerol (DAG) & Inositol trisphosphate ( IP 3 ) IP 3 mobilizes Ca ++ from ER Ca ++ and DAG activates tyrosine kinase C Tyrosine kinase C phosphorylate specific protein for physiological action 27 MECHANISMS OF HORMONE ACTION 28 Janus kinase = JAK Signal Transducer and Activator of Transcription = STAT ENZYME-LINKED HORMONE RECEPTORS MECHANISMS OF HORMONE ACTION 29 Sequence of Steroid hormone action: Endocrine gland secretes steroid hormones. Steroid hormone diffuses through target cell membrane and enters cytoplasm or nucleus. Hormones combines with a receptor molecule in the cytoplasm or nucleus. Steroid hormone-receptor complex binds to DNA and promotes transcription of messenger RNA. Messenger RNA enters the cytoplasm and directs protein synthesis. Newly synthesized proteins produce the steroid hormones specific effects. REFERENCES Human physiology, Lauralee Sherwood, seventh edition. Text book physiology by Guyton &Hall,11 th edition. Physiology by Berne and Levy, sixth edition. 30