Unit 1: Cell Signalling, Action of Hormones PDF

Unit 1: Cell signalling, action of hormones Dr. Elham Sharif, PhD Assistant Professor of Biomedical Sciences College of Health Sciences Qatar University Dr Elham Sharif...

Unit 1: Cell signalling, action of hormones Dr. Elham Sharif, PhD Assistant Professor of Biomedical Sciences College of Health Sciences Qatar University Dr Elham Sharif 1  Objectives After attending a lecture on Cell signalling, action of hormones, the student will: Take general notes about the endocrine system (TL1) Define Hormones and state their functions (TL1) Classify the types of signalling. (TL1) Categorize the different types of the hormones. (TL2) Diagram the general feedback mechanism for the hypothalamic pituitary axis. (TL2) Demonstrate how do hormones exert their action on the target cells. (TL2) Dr Elham Sharif 2  Hormones http://www.youtube.com/watch?v=kIPYVV4a ThM Dr Elham Sharif 3  The nervous system exerts point-to-point control through nerves, similar to sending messages by conventional telephone. Nervous control is electrical in nature and fast The endocrine system broadcasts its hormonal messages to essentially all cells by secretion into blood and extracellular fluid. it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone in order to respond Dr Elham Sharif 4  Releasing GH, ACTH, Thyroxine,andTSH, Estrogen, Cortisol,inhibiting FSH calcitonin, Testosterone Parathyroid Insulin epinephrine progesterone andand Hormones (TRH) LH, prolactin triiodothyronine Oestrogen norepinephrine testosterone hormone glucagon (for sensitivity) Hypothalamus TRH,GRH,etc Pituitary Gland TSH Thyroid Glands Parathyroid gland Pancreas Adrenal glands Testes Ovaries Dr Elham Sharif 5  Hormones are chemical messengers A given hormone usually affect only a limited number of cells, which are called target cells. Receptors on cells interact with the hormone. 6 Dr Elham Sharif Dr Elham Sharif 7 Types of cell signalling  Types of signalling P paracrine – hormone acts locally by diffusing from source to target cells in the neighbourhood A autocrine – the hormone acts on the same cell that produced it E endocrine – hormone distributed in blood and binds to target cell Dr Elham Sharif 9  Hormones are categorized into Four structural groups Peptides and proteins Steroids Amino acid derivatives Fatty acid derivatives Dr Elham Sharif 10  Peptides and proteins Can be secreted in one of two pathways Regulated secretion – cell stores hormone in Secretory granules - releases in bursts Constitutive secretion – cells do not store hormone but secretes it from secretory vesicles as it is synthesized Dr Elham Sharif 11 update Proteins & Peptides hormones Protein hormones: Synthesized by anterior pituitary, placenta, pancreas, and parathyroid glands 2) Synthesized, then stored in the cell as secretory granules until needed 3) Do not need carrier proteins to enter blood; water soluble 4) Clinically significant hormones include: (FSH), (LH), (TSH), (hCG), insulin, glucagon, parathyroid hormone, growth hormone, and prolactin. a) Glycoprotein hormones, FSH, LH, TSH, and hCG, composed of alpha and beta chains; alpha chains identical and beta chains unique for each hormone b) Peptide hormones synthesized as prohormone, cleaved to produce circulating hormone (e.g., insulin) 5) Mechanism of action: Protein hormones interact with a cell membrane receptor. This activates a second messenger system and then cellular action. 6) Hormone synthesis is regulated through change in analyte concentration in serum (e.g., insulin/glucose) and negative feedback by another hormone (e.g., testosterone/FSH).  Hormones are categorized into Four structural groups Peptides and proteins Steroids Amino acid derivatives Fatty acid derivatives - Eicosanoids Dr Elham Sharif 13  Steroid hormones Steroids are lipids and more specifically, derivatives of cholesterol (e.g. testosterone, cortisol) Cholesterol Mito and ER Steroid hormones Bind to DNA Dr Elham Sharif 14  update Steroid hormones 1) Synthesized by adrenal glands, gonads, and placenta 2) Synthesized from cholesterol as needed, not stored, lipid-soluble 3) Need a carrier protein to circulate in the blood 4) Clinically significant hormones includes: cortisol, aldosterone, testosterone, estrogen, and progesterone. 5) Mechanism of action: Free hormone is transported across cell membrane to interact with intracellular receptor; complex binds to chromatin, producing mRNA; mRNA initiates production of proteins that carry out the function attributed to the specific hormone. 6) Hormone synthesis is regulated through negative feedback by another hormone (e.g., cortisol/ACTH).  Hormones are categorized into Four structural groups Peptides and proteins Steroids Amino acid derivatives Fatty acid derivatives Dr Elham Sharif 16  Amino acid derivatives A. Thyroid hormones – thyroid gland B. Catecholamines: from adrenal medulla Norepinephrine Epinephrine 17 Dr Elham Sharif update Amine hormones 1) Synthesized by thyroid and adrenal glands 2) Synthesized from amino acids 3) Some amine hormones require a carrier protein and others do not. 4) Clinically significant hormones include epinephrine, norepinephrine, thyroxine, and triiodothyronine. 5) Mechanism of action: Epinephrine and norepinephrine do not bind to carrier proteins and interact with the receptor site on the cell membrane. Thyroxine and triiodothyronine circulate bound to carrier proteins, with the free hormone being transported across the cell membrane to interact with the intracellular receptor. 6) Hormone synthesis is regulated by nerve stimulation, another hormone (e.g., thyroxine/TSH), and negative feedback. 7. Methods for quantifying hormones need to be sensitive because of the extremely low levels of hormones in the circulation. enzyme-multiplied immunoassay technique (EMIT), fluorescent immunoassay (FIA), fluorescent polarization immunoassay (FPIA), chemiluminescent immunoassay (CLIA), electrochemiluminescence immunoassay (Electro CLIA), and high- performance liquid chromatography (HPLC).  Hormones are categorized into Four structural groups Peptides and proteins Steroids Amino acid derivatives Fatty acid derivatives Dr Elham Sharif 19  Fatty acid derivatives - Eicosanoids Eicosanoids are a large group of molecules derived from polyunsaturated fatty acids This group includes: prostaglandins, prostacyclins, Leucotrienes and thromboxanes. Dr Elham Sharif 20  Name the endocrine organs and the hormones they release What is a hormone? What does a hormone need to interact with a cell and basically how does this work? Name the groups of hormones Give an example of each group of hormone Dr Elham Sharif 21  Control of endocrine activity Dr Elham Sharif 22  Control of Endocrine activity Rate of production: Control is mediated by positive and negative feedback circuits Rate of delivery: eg blood flow to a target organ or group of target cells Rate of degradation and elimination: Have characteristic rates of decay, and are metabolized and excreted from the body through several routes Dr Elham Sharif 23  Long loop Short loop + positive feedback =stimulation -negative feedback = inhibition=stop release Example 1 Feedback control Neurons in the HT secrete TRH, which stimulates cells in the AP to secrete TSH +ve -ve TSH binds to receptors on epithelial cells in the TG, stimulating synthesis and secretion of TH, which affect +ve -ve almost every cell When TH increase above a certain threshold inhibition occurs Dr Elham Sharif 25 Example 2  Hormones invoke profound changes within target cells. How is this accomplished? Dr Elham Sharif 27 How do hormones change their target cells? By the Receptors Dr Elham Sharif 28  How do hormones change their target cells? By the Receptors Location of Classes of Principle Mechanism of Action Receptor Hormones Cell surface Proteins and Generation of second receptors A) (extracellular peptides, messengers which alter the catecholamines and activity of other molecules - receptors) (plasma eicosanoids usually enzymes - within the cell membrane) Intracellular B) receptors Steroids and Alter transcriptional activity of (cytoplasm and/or thyroid hormones responsive genes nucleus) Dr Elham Sharif 29  A) Cell surface receptors using 2nd messenger Second Examples of Hormones Which Messenger Utilize This System Epinephrine and norepinephrine, glucagon, luteinizing hormone, follicle stimulating hormone, Cyclic AMP thyroid-stimulating hormone, calcitonin, parathyroid hormone, antidiuretic hormone Protein kinase Insulin, growth hormone, prolactin, oxytocin, activity erythropoietin, several growth factors Epinephrine and norepinephrine, angiotensin II, Calcium and/or antidiuretic hormone, gonadotropin-releasing phosphoinositides hormone, thyroid-releasing hormone. Cyclic GMP Atrial naturetic hormone, nitric oxide Dr Elham Sharif 30  http://www.youtube.com/watch? v=NMeBZlbs2dU Dr Elham Sharif 31  Hormones with intracellular receptors B) Steroid hormone using Transcription factors Dr Elham Sharif 32  http://www.youtube.com/watch?v=oOj04WsU9ko Dr Elham Sharif 33  QUIZ The concentration of hormone as seen by target cells is determined by three factors -name them What is feedback control and give an examples What are the two principle mechanisms of action of hormones Give examples of the above Name two secondary messengers Dr Elham Sharif 34  THANK YOU Dr Elham Sharif 35