BMN 1002 Cell Biology Lecture 25: Introduction to Endocrinology PDF

BMN 1002 Cell Biology Lecture 25: Introduction to Endocrinology Dr. Ratnadeep Saha [email protected] Acknowledged to Dr David Kennedy Recommended textbook  Learning outcomes Define the endocrine system and hormones List the different clas...

BMN 1002 Cell Biology Lecture 25: Introduction to Endocrinology Dr. Ratnadeep Saha [email protected] Acknowledged to Dr David Kennedy Recommended textbook  Learning outcomes Define the endocrine system and hormones List the different classes of hormones and their properties Explain how the actions of individual hormones are mediated via receptors Explain the feedback principle for regulating hormone secretion  Mode of communication Paracrine & GAP junctions Synaptic Autocrine Endocrine cnearby cell and own cell) Message Message Message Message transmitted transmitted transmitted by transmitted directly from across - diffusion in by circulating cell to cell. synaptic cleft. interstitial fluid. - body fluids.Cbloodstream Specificity Specificity Specificity Specificity depends on depends on depends on depends on anatomical anatomical receptors. receptors. location. location and ex : heart receptors. making it - more specific  The endocrine system Endocrine – Greek words: – ‘endo’ : inside/within and ‘crinis’ : secrete What does it mean by an endocrine gland? Current awareness is that hormones may be produced in many tissues and have both local and distant effects. endecrie Glands (classical hormones Non-classical producers: Kidney Heart muscle Adipocytes Endothelium Platelets ~ The endocrine system and hormones Classical definition of the endocrine system: Endocrine cells within endocrine glands release substances (hormones) which are conveyed by the blood stream and act on distant cells t unt Hormone: cataintent ↳ Chemical messenger, synthesised by specialised cells, secreted into the blood in small amounts which acts on a specific receptor in target organs to regulate cellular function. *Endocrine signalling Synaptic signalling Relatively slow – relies Relatively greater on diffusion and blood - speed and precision – - flow - and travel a long distance in a very short - Hormones are greatly time - diluted in the bloodstream Neurotransmitters are and interstitial fluid and diluted much less and therefore must be able to can achieve high local act at very low concentrations concentrations (typically < 10-8M) Neurotransmitter Cf Conc, ↓ dilution) receptors have a Target’s cells relatively low affinity receptors have indicating that they can relatively high - dissociate rapidly to affinity for their ligand - terminate a response. What is the difference between Neurotransmitter, Neurohormone and Pheromone? Neurotransmitter - Act , ↓ released by synaptic cleft ADM Neurohormone N to bloed - secreted by neurone Pheromone - secreted by animal for moting L for attraction Hormones act on target cells; binds to specific receptors located either on the cell surface or within the cell. High affinity: Hormones are effective at low concentrations - amplify hormone each other ~ Synergistic: The effect of two hormones is greater than one alone e.g. - thyroid hormone and norepinephrine on heart rate; oestrogens and androgens act synergistically with FSH to enhance follicular proliferation and differentiation. chance the action of another hormon. one hormone Permissive: The presence of one hormone is necessary for another to have a full effect e.g. the effect of cortisol on glucagon's ability to increase blood glucose concentration during fasting; Estrogen stimulates initial thickening of endometrium, progesterone further increases thickness Antagonistic: Two hormones oppose each other’s effects e.g. insulin vs - glucagon hormones compete for same receptor ~ Competitive: Two hormones, similar in structure, compete for the same - - receptor e.g. epinephrine and norepinephrine. Classes of hormone and their properties Classes of hormone: There are three classes of hormone based on chemical structure. 1. Steroids e.g. oestrogen Synthesised from cholesterol 2. Peptides - - protein based va 2nd messegen act surface receptor on e.g. insulin Synthesised from amino acids 3. Amino acids made of action vary -. e.g. thyroid hormone Synthesised from tyrosine Note: Peptide and amino acid hormones are sometimes classed together (both have amino acids as a building blocks), thus giving 2 major classes of hormone.  Classes of hormone and their properties steroid pass through plasma mem. 1. Steroids: X lipid-friendly Small hydrophobic (lipophilic) molecules synthesised primarily from cholesterol. eno storage) Released immediately following synthesis. - (need protein to bind to transport) Circulate in bound form. Act on intracellular receptors which Hormone - then bind to DNA (hormone response elements) and regulate gene - transcription. - but Have slowLlong lasting effects. - Receptor DNA Nucleus Plasma membrane Steroids example of deroid hormone Receptor mediated action of steroid hormones see , record Inhibitory protein complex i Hormone binding site heat share Transcription Hsp90 activating domain Hinge region DNA binding domain Steroid hormone Exposed DNA binding site H2N COOH  Peptides & amino acids 2. Peptides Peptide hormones are between 3 and 332 amino acids in length. Synthesised as preprohormones and - stored prior to release. Act on cell surface receptors then via 2nd messenger systems Al to cause effect in target cells. 3. Amino acid Hormone Amino acid hormones include Receptor thyroid hormone and epinephrine. G protein Most synthesised from tyrosine. 2nd messenger Stored for instant release. (e.g. cAMP, IP3) Different modes of action (TH Cellular effects has intracellular receptor, others act at surface). Plasma Target cell membrane  Peptides & amino acids Pituitary Growth hormone, TSH, vasopressin Lecture 26 Hypothalamus TRH, LHRH Thyroid T3,, TT44 Lecture 27 Parathyroid Parathyroid hormone Adrenal medulla Epinephrine Lecture 28 Pancreas Insulin, glucagon Pineal gland Melatonin Placenta Chorionic gonadotrophin Liver Angiotensin (angiotensinogen) GI tract Gastrin, cholecystokinin, somatostatin Kidney Erythropoietin Heart Atrial natriuretic peptide Action on receptors & 2nd messengers: Peptide & amino acid hormones serpentine Hormone Receptor Ion channel Coupling factors G proteins activates Second messengers cAMP cGMP Ca2+ Diacylglycerol IP3 activates Third messengers Protein phosphorylation Protein kinase cadd phosphate) Dephosphoprotein Phosphoprotein Protein phosphatase cremore phosphate) Multiple physiological - responses Rapid Short-term Long-term e.g. Transporter protein e.g. General metabolism, e.g. Regulation of activation or inhibition. neurotransmitter synthesis/release gene expression. and receptor sensitivity. Action on receptors & M cAMP: Peptide & amino acid hormones - Hormone Heterotrimeric G protein serpentine β activates Effector Receptor α - α adenylyl cyclase γ GDP GTP activated and activates adenyly cyclase activets Protein Kinase R R 2nd messenger A C cAMP C P P Enzymes P Transcription AAAAA Translation  Action on receptors &O IP3: Peptide & amino acid PlP2-DAGActivate hormones Signal molecule Phosphatydyl De - inositol - IPS-sacro- bisphosphate plasmic Diacylglycerol reticulune Activated (PIP2) Ca2 Receptor (DAG) - release Phospholipase C ↓ for ↳ muscle. Activated protein Kinase C (PKC) Activated G Inositol trisphosphate protein (IP3) GDP- GTP IP3 activated Ca2+ bind channel Sarcoplasmic reticulum Ca2+ activates and releases Chormone stimulatecGMP Enzyme Linked Receptor - like insulin * receptor amino acid ↳ membrane bed - ↳ extracellular -  Mechanisms for hormone release, activation D and feedback control Hormone release Continuous: e.g. Thyroid hormone under control of TSH. Pulsatile: e.g. GHRH, GnRH (released every 90-120 mins). ↓ & pulses released night Circadian: e.g. Melatonin.atto sleep & within 24 hour Exocytosis on stimulus: e.g. insulin. Hormone activation all steroids T undergo Post release modification: modification secreted Steroids - oestrogensLfrom androgens Vitamin D -[Skin to liver (HCC) and then travels to kidney (DHCC): the most effective form] Angiotensinogen (Liver) → Angiotensin I ( by Renin in kidney) → Angiotensin II (by angiotensin converting enzyme in lung)  Mechanisms for hormone release, activation and feedback control Control of hormone effects structural alteration Modification: Increases/decreases hormone activity e.g. Vitamin D Degradation: Hormone broken down or excreted e.g.oestrogen creducting hormones Receptor down-regulation: e.g. adrenergic receptors Termination of intracellular effects: e.g. phosphatases - Negative feedback: By the regulated metabolite (e.g. glucose/insulin) By the hormone itself (e.g. cortisol, TH) By the trophic hormone released by the pituitary CACTH) Feedback control: Simple feedback e.g. glucose homeostasis by insulin Drop in blood glucose Increase in blood glucose Response Increase in blood glucose Drop in blood glucose stimulate Increase in glucose uptake Decrease in glucose uptake Pancreas Increased insulin production Insulin responsive Decreased insulin production cells Integrated and complex system! previousdide Attempt few questions in VEVOX in the session Extra slides showing hormones that follows different 2nd messenger system: Receptor mediated action of peptide and amino acid hormones: cAMP G Receptor mediated action of peptide and amino acid hormones: IP 3 O · g