Lecture 02 – Endocrine System PDF

MED1001 Human Physiology Lecture 02 – Endocrine System 11th September, 2024 Dr TSANG Chi Ching (MHS) [email protected]  2 Learning Foci Compositions & actions of hormones Co...

MED1001 Human Physiology Lecture 02 – Endocrine System 11th September, 2024 Dr TSANG Chi Ching (MHS) [email protected]  2 Learning Foci Compositions & actions of hormones Contributions of hormones to homeostasis Functions of hypothalamus & pituitary gland ▫ Also their hormones Production, regulation & effects of thyroid hormone & cortisol 3  4 Chemical Messengers Intercellular communication  5 Endocrine Glands Hormones are secreted by ▫ Endocrine glands  cf. Exocrine glands ▫ Hormone-secreting cells are located in various organs, e.g.  Brain  Heart Secretion  Kidneys Interstitial fluid  Liver  Stomach  6 Adapted. adrenaline noradrenaline  7 Adapted. (W08) Adrenaline noradrenaline (Epinephrine) (norepinephrine) (W07 & W08) (W14) (W05, W06 & W10)  8 (W05, W06 & W10) (W07 & W08) (W10)  9 (W14) (W05, W06 & W10)  10 Classes of Hormones 3 major structural classes ▫ Amines  Organic molecules with functional group(s) which contain a basic N atom with a lone pair of electrons ▫ Peptides & proteins ▫ Steroids  Lipids with a special structure composed of 4 interconnected rings of C atoms  ‘Skeleton’  11 Amines Amino acid derivatives ▫ e.g. From tyrosine, tryptophan, etc. Adapted. © Rye C et al. Biology 2e. 2018. Houston: OpenStax. Adrenaline (Epinephrine)  12 Adapted. Amines Thyroid hormones Adapted. © California Office of Environmental Health Hazard Assessment. ▫ Thyroid gland Catechol Catecholamines ▫ Hypothalamus  Dopamine Noradrenaline (Norepinephrine) ▫ Adrenal medulla of adrenal glands  Adrenaline (epinephrine)  Noradrenaline (norepinephrine) Adrenaline (Epinephrine)  13 © The Johns Hopkins University, The Johns Hopkins Hospital, and Johns Hopkins Health System Adrenaline & Noradrenaline Adrenal medulla ▫ Expresses high amount of PNMT (phenylethanolamine-N-methyltransferase) Adapted. (PNMT) Noradrenaline Adrenaline (Norepinephrine) (Epinephrine) ▫ Secretes 4 times more adrenaline than noradrenaline  14 Peptides & Proteins Most hormones are polypeptides Adapted. Exocytosis (Linear polypeptide) (Folded into proper configuration) (Post-translationally modified)  15 Peptides & Proteins Adapted. e.g. Proinsulin (intramolecular disulphide bond) Secreted into blood by pancreas (key regulator of metabolism) in roughly equimolar amount (bioactive effect on microvascular blood flow & tissue health) + 4 amino acid residues which are removed  16 Steroids Primarily produced by adrenal cortex, gonads (testes & ovaries) & placenta (during pregnancy)  17 Steroids Synthesis triggered by G protein-coupled receptor signalling (Cyclic AMP) (Cyclic AMP) Caffeine (coffee) (Protein kinase A) (Protein kinase A) & theophylline (tea): inhibitors  18 Hormone from anterior pituitary gland Steroids In plasma, reversibly bind to carrier proteins such as albumin for circulation (Protein kinase A) Taken up from extracellular fluid or synthesised intracellularly  19 Adapted. Steroids Adrenal cortex ▫ Five major hormones Adrenaline noradrenaline Androgens (glucocorticoid & weak mineralocorticoid) (glucocorticoid) (mineralocorticoid)  20 Steroids Adapted. Gonads Same androgen pathway as in adrenal cortex Oestrogens (mainly) (mainly)  21 Signalling Mechanism of Water-Soluble Hormones Second messengers (e.g. cAMP) © Gordon Betts J et al. Anatomy and Physiology 2e. 2022. Houston: OpenStax.  22 Signalling Mechanism of Water-Soluble Hormones Second messengers (e.g. Ca2+)  23 Signalling Mechanism of Water-Soluble Hormones Enzyme activation by receptor (e.g. Janus kinase [JAK])  24 Signalling Mechanism of Water-Soluble Hormones Intrinsic enzymatic activity of receptor (e.g. tyrosine kinase)  25 Signalling Mechanism of Lipid-Soluble Hormones © Gordon Betts J et al. Anatomy and Physiology 2e. 2022. Houston: OpenStax.  26 Hormones Water-soluble, dissolved in plasma Poorly soluble Hormone/Protein complex ⇌ Free hormone + Carrier protein  27 © Hall, JE. Guyton and Hall Textbook of Medical Physiology. 12th Ed. Philadelphia: Saunders Elsevier. Hormones  28 © Hall, JE. Guyton and Hall Textbook of Medical Physiology. 12th Ed. Philadelphia: Saunders Elsevier. Hormones (Noradrenaline) (Adrenaline)  29 © Hall, JE. Guyton and Hall Textbook of Medical Physiology. 12th Ed. Philadelphia: Saunders Elsevier. Hormones  30 Metabolism & Excretion of Hormones  31 Hormonal Actions Hormones are transported in blood ▫ They can reach all body tissues ▫ Yet, response to hormone is highly cell-type specific Prolonged exposure to low concentration of hormone ▫ May lead to upregulation of corresponding receptors Exposure to high concentration of hormone ▫ May lead to downregulation of corresponding receptors  32 Hormonal Actions Adapted. Adrenaline Hormones can down-/up- Adrenaline regulate receptors for other hormones, too ▫ Down-regulation  Reduce effectiveness of 2nd hormone ▫ Up-regulation  Increase effectiveness of 2nd Adrenaline hormone  Permissiveness Adrenaline  33 Control of Hormone Secretion 3 types of control factors Or paracrine substances in Adapted. interstitial fluids (in plasma) (in plasma) Neuronal signals >1 input can influence hormone secretion ▫ Multiple regulatory systems  34 Control of Hormone Secretion Plasma [mineral ions / organic nutrients] ▫ e.g. Insulin  35 Control of Hormone Secretion Neuronal signals Adapted. (adrenaline)  36 Control of Hormone Secretion Other hormones ▫ Tropic hormones  Hormones which influence/control secretion of other hormones  Usually stimulatory, some inhibitory  May also be trophic in nature  Stimulate growth of stimulated glands 37  38 Hypothalamus & Pituitary Gland (major supply of blood to anterior pituitary gland)  39 Posterior Pituitary Hormones Posterior pituitary is not a ‘gland’ ▫ It does not synthesise hormones which are released from it ▫ Two hormones are released to the circulation  Produced & secreted from neurones from supraoptic & paraventricular nuclei of hypothalamus  Oxytocin & vasopressin Posterior pituitary is also called neurohypophysis © Borrow AP et al. Posterior pituitary hormones. In: Hormonal Signaling in Biology and Medicine. Comprehensive Modern Endocrinology. Litwack G (ed.). London: Academic Press. pp 203-226.  40 Posterior Pituitary Hormones Oxytocin ▫ Involved in two reproduction reflexes  Cervical stretch reflex  Milk ejection reflex Vasopressin ▫ Also called antidiuretic hormone (ADH) ▫ Involved in regulation of blood pressure & fluid balance  41 Anterior Pituitary Gland Hormones Anterior pituitary ▫ Also called adenohypophysis Hypophysiotropic hormones Secretion of anterior pituitary gland hormones are controlled by hypothalamus Usually three-hormone system ▫ Exception: dopamine/prolactin axis ▫ This allows signal amplification  42 Anterior Pituitary Gland Hormones Gonadotropins Adrenocorticotropic Follicle-stimulating Luteinising hormone hormone hormone Thyroid-stimulating hormone (Corticotropin)  43 Hypophysiotropic Hormones Hypothalamic neurones end in median eminence Hypophysiotropic hormones do not go into general circulation directly ▫ They enter hypothalamo- hypophyseal portal vessels & are brought to anterior pituitary gland  This ensures that hypophysiotropic hormones can reach cells of anterior pituitary gland without delay  The small total blood flow in portal vessels allows small amounts of hypophysiotropic hormones from a few hypothalamic neurones to control secretion of anterior pituitary hormones without dilution in systemic circulation  44 Hypophysiotropic Hormones  45 3-Hormone Systems  46 Control of Hypophysiotropic Hormones Secretion Neural control ▫ Stimulatory & inhibitory input from CNS ▫ Circadian regulation  Neural input from other regions of hypothalamus  Linked to visual signals: presence/absence of light © Vis DJ et al. Detecting regulatory mechanisms in endocrine time series measurements. PLoS One. 2012;7(3):e32985.  47 Control of Hypophysiotropic Hormones Secretion Hormonal feedback Non-sequence hormones ▫ Can also influence secretion of hypophysiotropic or anterior pituitary hormones  e.g. Oestradiol can enhance prolactin secretion from anterior pituitary  Even though oestradiol secretion is not controlled by prolactin 48  49 Adapted © Hall, JE. Guyton and Hall Textbook of Medical Physiology. 14th Ed. 2021. Philadelphia: Elsevier. Thyroid Gland  50 © Hershman JM, Merck Sharp & Dohme Corp. MSD Manuals. Overview of Thyroid Function. T3 & T4 Thyroid peroxidase (MIT) (DIT) (Iodide trapping) (Thyroxine) (Na+-dependent Cl−/I− transporter) (Coupling)  51 Control of Thyroid Function Stimulus: low blood levels of T3 and T4 or low metabolic rate  52 Actions of Thyroid Hormones Change © Hall, JE. Guyton and Hall Textbook of Medical Physiology. 14th Ed. 2021. Philadelphia: Elsevier. 53  54 Cortisol: Stress Hormone Stress ▫ Real or perceived threat to homeostasis, e.g.:  Trauma  Infection  Intense heat/cold  Physical restrain  Change in water intake  Pain  Sleep deprivation  Other emotional stresses  55 Control of Cortisol Secretion  56 Physiological Effects of Cortisol Adapted. noradrenaline (norepinephrine)  57 Other Stress-Related Hormones Adrenaline & noradrenaline ▫ Produced by chromaffin cells in adrenal medulla ▫ Secreted in response to sympathetic stimulation ▫ Intensify sympathetic responses © Carmichael SW & Winkler H. The adrenal chromaffin cell. Scientific American. 1985. 253:40–49.  58 Adapted. © Tortora GJ & Derrickson B. Principles of Anatomy & Physiology. 14th Edition. Hoboken: John Wiley & Sons. Stress Response Hormonal responses Neural Responses (Internal organs) Adrenaline and noradrenaline Prepare the body to fight or flee. Non-essential body functions (e.g. digestive, urinary & reproductive activities) are inhibited. (Immediate) (Long-term)  59 Additional information for reference  60 Additional information for reference Growth Cell division & net protein synthesis Growth in height ▫ Specifically determined by bone growth  Especially the vertebral column and legs  Epiphyseal growth plate  Actively proliferating cartilage  Chondrocytes  Lay down new cartilage in the interior of the plate  Osteoblasts at the shaft edge  Convert cartilaginous tissue at the edge to bone  Linear growth of the shaft  61 Additional information for reference Growth (long-bone and vertebral growth)  62 Additional information for reference Hormonal Influences on Growth Growth hormone Insulin Insulin-like growth factors (IGF) 1 & 2 Thyroid hormone Sex hormones (testosterone, oestradiol) Cortisol etc.  63 Additional information for reference Growth Hormone Little effect on foetal growth Most important hormone for growth after 1–2 years of age Stimulate cell divisions in many target tissues ▫ Major growth-promoting effect ▫ e.g. Stimulates maturation & cell division of chondrocytes  Widens epiphyseal plates & provides more cartilaginous material for bone formation  Bone lengthening  64 Additional information for reference Growth Hormone Induces IGF-1 synthesis in and secretion by liver ▫ IGF-1 enters blood circulation and functions as a hormone Induces bone cells to secrete IGF-1, too ▫ Here IGF-1 functions as an autocrine/paracrine substance  65 Additional information for reference Growth Hormone & IGF-1 1. GH stimulates prechondrocytes & young differentiating chondrocytes in epiphyseal plates to differentiate into chondrocytes 2. Differentiating chondrocytes begin to secrete IGF-1 and become responsive to IGF-1 3. Autocrine/paracrine IGF-1 & blood-borne IGF-1 stimulate differentiating chondrocytes to undergo cell division  66 Additional information for reference Growth Hormone Stimulates protein synthesis in various tissues & organs ▫ In particular: muscles ▫ By increasing amino acid uptake, synthesis of ribosomes & activity of ribosomes  Enlargement of tissues & organs  67 Additional information for reference Growth Hormone  68 Additional information for reference Control of Growth Hormone Secretion  69 Additional information for reference Control of Growth Hormone Secretion © Hall, JE. Guyton and Hall Textbook of Medical Physiology.  70 Additional information for reference Control of Growth Hormone Secretion GH secretion occurs in episodic bursts & manifests as a daily rhythm During most of the day, little or no GH is secreted ▫ Burst may be elicited by certain stimuli (e.g. exercise) 1–2 hours after falling asleep, one or more larger, prolonged bursts of GH secretion occurs  71 Additional information for reference IGFs IGF-1 ▫ Needed for normal foetal total-body growth & normal maturation of foetal nervous system ▫ Secretion stimulated by placental lactogen  Share sequence & structural similarities with GH IGF-2 ▫ Secretion independent of GH ▫ Crucial during prenatal period, but function not yet defined ▫ May also help maintain skeletal muscle mass & strength in the elderly  72 Additional information for reference Insulin An anabolic hormone Promote transport of glucose & amino acids from extracellular fluid into adipose tissue and skeletal & cardiac muscle cells Stimulate fat storage Inhibit protein degradation ▫ Important for growth Stimulates cell differentiation & division during foetal life and childhood ▫ Direct growth-promoting effects  73 Additional information for reference Thyroid Hormone Facilitates synthesis of GH Stimulates chondrocyte differentiation, growth of new blood vessels in developing bones & responsiveness of bone cells to other growth factors (e.g. fibroblast growth factor)  74 Additional information for reference Sex Hormones Testosterone & oestradiol Secretion begins to increase just before puberty Pubertal growth spurt ▫ Growth of long bones & vertebrae Stimulates GH & IGF-1 ▫ Major growth-promoting effect Also induce epiphyseal closure ▫ Stop bone growth ultimately ▫ ‘Dual effect’  75 Additional information for reference Testosterone Also stimulates protein synthesis in non-reproductive organs & tissues ▫ Direct anabolic effect ▫ Muscle mass higher in men than in women  76 Additional information for reference Cortisol Potent antigrowth effect Inhibits DNA synthesis Stimulates protein catabolism Inhibits bone growth & breaks down bone Inhibits GH & IGF-1 secretions  77 Additional information for reference Growth-Related Hormones  78 Additional information for reference  79 Additional information for reference Circadian Rhythm Synchronisation to day–night cycle is mediated by the suprachiasmatic nucleus (SCN) in hypothalamus via the retinohypothalamic tract (RHT) SCN neurones ▫ ‘Circadian pacemakers’ Retinal input © Hastings MH et al. Generation of circadian rhythms in the suprachiasmatic nucleus. Nat Rev Neurosci. 2018;19(8):453-469.  80 Additional information for reference Pineal Gland & Melatonin Superior cervical ganglion Intermediolateral nucleus (spinal cord) Paraventricular nucleus (hypothalamus) Suprachiasmatic nucleus © Cornell B, BioNinja. Melatonin. 2016. http://ib.bioninja.com.au/ © Borjigin J et al. Circadian regulation of pineal gland rhythmicity. Mol Cell Endocrinol. 2012;349(1):13-19.  81 © RajaratnamAdditional SM, Arendt J. information for reference Lancet. 2001;358(9286):999-1005. Pineal Gland & Melatonin © Lanser L et al. Inflammation-induced tryptophan breakdown is related with anemia, fatigue, and depression in cancer. Front Immunol. 2020;11:249.  82 Additional information for reference Melatonin © Brzezinski A. Melatonin in humans. N Engl J Med. 1997;336(3):186-195.