Endocrine system After studying this chapter, students are able to know: −the difference between endocrine and neural control − different types of intercellular chemical signals and signallings − to differentiate between endocrine and exocrine glands − Hormones, chemical classes of hormones define their properties: Hormonetarget cell interactions Signal transduction pathways triggered by hormones −Hormone-receptor interaction − Membrane-bound receptors for lipophobic hormones − signal transduction pathways with the 2nd messenger system: cAMP,c GMP, IP3, DAG, Ca2+ − intracellular receptors for lipophilic hormones and the regulation of gene expression and protein synthesis −The main endocrine glands/ tissues /structures in human − The hypothalamus-pituitary-target gland axis and negative feedback control of endocrine glands −Hypothalamus and neurohormones − Pituitary gland and its hormones −Thyroid gland and thyroid hormones The synthesis of thyroid hormones, the role of iodine in the synthesis of thyroid hormones Hyper-and hypothyroidism − Parathyroid gland and the role of its hormones in regulating blood calcium concentration −Adrenal gland, corticosteroid hormones and catecholamines − Pancreas gland Insulin, glucagon and diabetes mellitus − Sex hormones and functions Specific terms and keywords • • • • • • • • • • Endocrine Endocrine glands/exocrine gland Endocrinology Hormone Hormone synthesis Hormone release/secretion Receptor Hormone-receptor interaction Target cells Signal transduction pathway Endocrine system and nervous system - the two main control systems in the body • The endocrine system, together with the nervous system, work to control and coordinate the cells to accomplish physiological activities and function of animals • The endocrine system works differently from how the nervous system does: Neural control electrical signal and chemical signals fast - - Endocrine control chemical signals (hormones) slow , longer lasted Rõ ràng, xác - precisely targeted (neural signals are precisely targeted) - controls predominantly the fine, rapid movements of discrete muscles Phần lớn, chủ yếu • - broadcast (endocrine signals are broadly distributed throughout the animal’s body) controls more widespread, prolong activities (e.g.metabolic changes) The nervous system and the endocrine system can control one another Endocrine signal is one type of intercellular chemical signals Autocrine signal Neurohormone Paracrine signal Neurotransmitter Endocrine signal Pheromone www.copewithcytokines.de/cope.cgi?key=Autocrine Endocrine and Exocrine glands http://www.fotosearch.com/comp/LIF/LIF115/SA401031.jpg Hormone and its properties • Hormone is a chemical substance produced and released by endocrine cells or by neurons It regulates function of distant cells reached via the blood • Hormones are chemical messengers transporting signal from one cell to another -> they convey information from cells to cells • Hormone is effective at very low concentration (e.g.for insulin: 1IU= 0.0347 mg • Hormones are secreted by secretory cells into extracellular fluid, from which they diffuse into capillaries and the circulation They travel in the blood to reach distant target cells/ tissues expressing specific receptors • Hormones trigger cascade effect in the target cells hormonal signal is amplified by hormonal cascade effects C.L Standfield.2011 Principles of Human Physiology, 4th edition Hormone interactions • One hormone can target different cell types -> can produce more than one effect in the body (eg ADH affects epithelial cells in the kidneys (increasing water reabsorption) and smooth muscle cells of some blood vessels (causing vasoconstriction of these vessels) • One body function is regulated by more than one hormone (eg Blood Ca2+ is controlled by calcitonin, PTH, vitamin D3; blood glucose by insulin, glucagon, epinerphrine, cortisol, GH) • If the effects of hormones oppose each other: antagonism process • If or more hormones produce the same type of response, the effect can be addictive (net effect equals the sum of individual effects) or synergistic (net effect is greater than the sum of individual effects) • If the presence of one hormone is needed for another hormone to be effective: permissiveness process (e.g thyroid hormone stimulates beta adrenergic receptor expression needed for epinephrine to be effective on smooth muscle cells of bronchioles (dilating bronchioles) Sự co mạch chống chọi, phản đối Chemical classification of hormones Amino acids Glutamate, aspartate, glycine, gamma-aminobutyric acid (GABA) hydrophilic, lipophobic Amines Catecholamines: dopamine, norepinephrine, epinephrine (tyrosine derivatives) Thyroid hormones (tyrosine derivatives) Serotonine (tryptophan derivatives) Histamine (histidine derivatives) hydrophilic, lipophobic Peptides/ Proteins GH, Prolactin, Insulin / Thyrotropin releasing hormon, oxytocin, ADH, calcitonin, glucagon, ACTH, endorphin, MSH, Hormon hypothalamus, lipotropin, somatostatin Hydrophilic, lipophobic Glycoprotein FSH, LH,TSH,PTH Steroids Estrogen Progestin (progesterone) Testosterone Mineralocorticoid Glucocorticoid Hydrophobic, lipophilic Fatty acid Derivativatives of arachidonic acid: prostaglandins, leukotriens, thromboxanes Hydrophobic, lipophilic Properties of hormones depend mainly on whether they are lipophilic or lipophobic Calcitonin Tế bào C • Produced by C cells • Target organ: bone • Binds to membrane bound receptors -> decreases osteoclast activity, increases osteblast activity -> Ca, P plasma concentration Parathyroid gland • PTH (parathyroid hormone) • Target organs: bone, kidneys, intestines: increases Ca2+, decreases P plasma concentration • G-protein receptor-cAMP • stimulates osteoclast activity, increases Ca2+ reabsorption in renal tubules and in intestine • Increases renal P secretion 84 a.a, 95.000 http://www.univ-st-etienne.fr/lbti/Mednucl/AtlasEnd/parathy/abase5.htm The adrenal glands C.L Standfield.2011 Principles of Human Physiology, 4th edition • adrenal cortex • adrenal medulla: modification of a sympathetic ganglion Hormones of adrenal cortex • Steroid hormones, cholesterol derivatives • Bind to intracellular receptors, regulating gene expression and protein synthesis of target cells – Mineralocorticoid: • Aldosterone: increases Na+, H20 reabsorption, increases K+ secretion -> increases Na+, decreases K+ plasma concentration – Glucocorticoid • Cortisol: – Promotes energy mobilization and glucose sparing – Increases gluconeogenesis, stimulate protein breakdown in muscle, decreases glucose and amino acid uptake into cells, inhibits protein synthesis – At high doses: inhibits inflammation and allergic reactions – is increased in stress response: stress hormone – Is required for GH secretion and for normal responsiveness of blood vessels to vasoconstrictive stimuli (sympathetic, epinerphrine, angiotensin II) – Androgen • Testosterone Hormones of adrenal medulla • • • • Adrenaline (epinephrine) 80% Noradrenaline (norepinephrine) 20% Neurohormones, tyrosine derivatives Effects: – Increase blood glucose concentration – Increase heart rate, contractility in cardiac muscle, vasoconstriction The Hypothalamus-Pituitary-Adrenal (HPA) axis stress CRH mRNA Hypothalamic PVN CRH Glucocorticoid receptor POMC mRNA Λ Anterior pituitary POMC (Corticotrophs) ACTH Λ Steroidogenesis Adrenal cortex • CRH • ACTH Glucocorticoids (cortisol) ACTH receptor (MC2R) Interrenal-pituitary interaction in zebrafish To et al.Mol Endocrinol 2007 Feb;21(2):472-85 Pancreas gland • • • • Islet of Langerhans alpha cells (20%): glucagon beta cells (75%): insulin Delta cells: somatostatin Fig 6.10 C.L Standfield.2011 Principles of Human Physiology, th edition Insulin and its function C.L Standfield.2011 Principles of Human Physiology, 4th edition • • • • • • Reduces blood glucose concentration Influences energy metabolism: promote energy storage Affects the transport of nutrients across the membranes of all body cells except those in liver and CNS Stimulates amino acid uptake to cells facilitating protein synthesis Increases the number of glucose transporters (GLUT4), hence stimulates glucose uptake into cells Permissive to GH effects: the presence of insulin is needed for GH to be effective Glucagon • Is produced by anpha cells • Increases blood glucose concentration • Target tissues: liver, Adipose tissue C.L Standfield.2011 Principles of Human Physiology, 4th edition C.L Standfield.2011 Principles of Human Physiology, 4th edition Regulation of blood glucose concentration C.L Standfield.2011 Principles of Human Physiology, 4th edition Diabetes mellitus • Diabetes mellitus type (insulin dependent diabetes mellitus – IDDM) – – – – loss of the insulin-producing beta cells 3%, autoimmune disease (beta cell are destroyed) Occurred mainly in children adolescents Insulin injection • Diabetes mellitus type (NIDDM) – insulin resistance – occurred mainly in adults(40-45), 97% – Insulin injection, drugs promoting insulin secretion, tăng tác dụng insulin, diet, exercise Pineal gland and thymus gland • Pineal gland – Melatonin, Arginine vasotocin – Establishing circadian rhythm • Thymus gland – Thymosin: normal immune function, T cell function Reproductive glands • Male reproductive glands – the testes – Androgens: testosterone (produced by leydig cells) • Female reproductive glands – Ovary: estrogen – Corpus luteum: progesterone – Placenta: HCG (Human Chorionic Gonadotropin) [...]... hormone/ messenger or a class of messengers • The binding between a hormone and a receptor is a brief, reversible chemical interaction • Affinity: the strength of the binding between a messenger and its receptor C.L Standfield.2011 Principles of Human Physiology, 4th edition Hormone signal transduction pathway 1 signal reception 2 signal transduction 3 response of the target cell fig.cox.miami.edu/~cmallery/150/memb/cellcomm.htm... The 4-level control of endocrine system CNS + - Hypothalamus + Pituitary + - Target glands C.L Standfield.2011 Principles of Human Physiology, 4th edition The hypothalamus produces releasing and inhibiting hormones regulating pituitary hormone production and secretion • Hormones produced in the hypothalamus are neurohormones • Hypothalamus hormones are tropic/trophic hormones as they regulate the... receptors but do not produce a biological response • Antagonists may compete with agonists for the receptor, blocking or decreasing the effects of agonists on target cells application in drug design and drug target Location of receptors in target cells • • Location of receptors in target cells depends on whether the messenger/hormone is lipophilic or lipophobic membrane bound receptor – Lipophobic/hydrophilic... activate G protein • intracellular receptor – receptors in cytosol or in the nucleus of target cells – Lipophilic (lipid-solube) hormones Fast ligand-gated calcium channels Fig 5.13 C.L Standfield.2011 Principles of Human Physiology, 4 th edition enzyme-linked receptor • The receptor and the enzyme (mainly tyrosine kinase) are the same protein • H-R changes enzyme conformation-> activate tyrosine kinase... G-proteine-linked receptor • 7 transmembrane domains • Extracellular side binds to hormone/ligand • Intracellular side binds G-protein(GDP) • When inactivated:Gprotein: α, β, γ; α –GDP • When activated: α –GTP moves to the effectors changing effectors activity • Effectors: ion channels (slow ligand gated ion channels) or enzymes • Slow ligand-gated ion channel Fig.5.15 C.L Standfield.2011 Principles of... protein (Gi protein) Gs and Gi proteins activate and inhibit, respectively, enzymes (amplifier enzymes) catalyzing the production of 2nd messengers • 2nd messengers: – – – – – cAMP (cyclic AMP) cGMP (cyclic GMP) Inositol triphosphate (IP3) Diacyglycerol (DAG) Ca2+ H- G-protein R -> Adenylate cyclase-> cAMP -> protein kinase A Earl W Sutherland (Nobel Prize - 1971) cAMP: epinephrine glucose C.L Standfield.2011...The synthesis of peptide/protein hormones Fig 5.4 C.L Standfield.2011 Principles of Human Physiology, 4 th edition C.L Standfield.2011 Principles of Human Physiology, 4th edition The release and transport of hormone in blood • H-Pr H + Pr C.L Standfield.2011 Principles of Human Physiology,... of Human Physiology, 4 th edition Beänh dòch taû Cholera C.L Standfield.2011 Principles of Human Physiology, 4th edition Lipophilic hormones cross the plasma cell membrane, binding to intracellular receptors, modulating gene expression and protein synthesis of target cells Fig 5.11 C.L Standfield.2011 Principles of Human Physiology, 4 th edition C.L Standfield.2011 Principles of Human Physiology,... receptor and channel are the same protein −Acetylcholin: Na+ (excitatory) −Serotonin: Na+ (excitatory) −Glutamat: Na+ (excitatory) −Glycine: Cl- (inhibitory) −GABA: Cl- C.L Standfield.2011 Principles of Human Physiology, 4th edition (inhibitory) G-proteine-linked receptor • 7 transmembrane domains • Extracellular side binds to hormone/ligand • Intracellular side binds G-protein(GDP) • When inactivated:Gprotein:... secretion of other hormones: – Releasing hormones stimulate hormone production and secretion of pituitary gland • PRH (prolactin releasing hormone): stimulates prolactin secretion • TRH (thyrotropin releasing hormone): TSH • GnRH (gonadotropin releasing hormone): FSH, LH • GHRH (growth hormone releasing hormone): GH • CRH (corticotropin releasing hormone): ACTH – Inhibiting hormones inhibit the secretion