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Endocrine System Lect # 1 Introduction Prof Kumlesh K. Dev Department of Physiology Chapter 4 Principles of Neural and Hormonal Communication Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Some learning outcomes • principles • types of chemical signals • receptors types • feedback eedbac regulation egu at o • major hormones • pituitary • hypothalamic • adrenal • hypothalamo-pituitary axis • hormonal regulation of • growth • glucose and metabolic • calcium Types of cellular communication Classification communication i ti iis critical iti l ffor cellll – survival – function two major communication systems: – nervous system – endocrine system Chapter 4 Principles of Neural and Hormonal Communication Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning Four types of chemical messengers Classification 1)) Autocrine/Paracrine • local chemical messengers • exert effect on neighbouring cells (paracrine) or on same cell (autocrine) 2) Neurotransmitter • short-range h t chemical h i l messengers • diffuse across narrow space (synapse) to act on adjoining dj i i ttargett cellll ((another th neuron, a muscle, or a gland) Four types of chemical messengers Classification 3)) Neurohormones • hormones released into blood by neurosecretory neurons • distributed through blood to distant target cells 4) Hormones • long-range l messengers • secreted into blood by endocrine glands in response to t appropriate i t signal i l and d actt on distant target cells 1. Autocrine/Paracrine Classification – chemical messenger released from a cell : Secretory Cell autocrine – can act on itself (autocrine) – can act on another cell close by (paracrine) close-by paracrine Cell #2 2. Neurotransmitters Classification – neurotransmitters released from synaptic y p vesicles – diffuse across synapse between b t two t cells synapse with muscles l – transmitter binds a receptor p – receptor activation stimulates ti l t the th cellll synapse with another neuron synapse with glands 3. Neurohormones Classification – released from synaptic vesicles by neuron – released into blood – acts in manner similar to hormones 4. Hormones Classification – messengers off endocrine system – released from endocrine g gland into blood – transported t t d in i blood bl d – target cell expresses specific receptors Nervous and Endocrine Communication Classification Property Nervous System Endocrine System Structure Wired system of neurons Wireless system of glands Chemical Messenger Neurotransmitter Hormones Target g site Veryy close Far awayy Distance of Action Across synaptic cleft Carried by blood Speed of Response milliseconds mins to hours Duration of Action milliseconds mins to days Major Function fast precise responses long duration responses Four Types of hormones Classification • Two hormone categories based on solubility – Hydrophilic (lipophobic, (lipophobic water soluble) • 1. Peptide hormones • 2. 2 Catecholamines C t h l i – Lipophilic (hydrophobic, (hydrophobic water insoluble) • 3. Thyroid hormone • 4. Steroid hormones Four Types of hormones Classification Property Peptide Catecholamine Thyroid Steriods Structure amino acids tyrosine derivative iodinated tyrosine cholesterol derivative Solubility hydrophilic lipophobic hydrophilic lipophobic lipophilic hydrophobic lipophilic hydrophobic Receptors on cell surface on cell surface inside cell inside cell Synthesis in ER in cytosol organelles intracell Storage granules granules colloid lipid droplets Secretion exocytosis of granules exocytosis of granules endocytosis of colloid diffusion Blood Transport free hormone plasma bound plasma bound plasma bound Hormone hypothalamic, pituitary, pineal, pancreas, parathyroid, GIT, kidney, liver, heart adrenal medulla thyroid follicular adrenal cortex gonads, Vit D Steroid hormone Synthesis ffemale l sex hormone male sex hormone adrenal cortex hormone - adrenal cortex hormone steroid hormones derived from cholesterol are small lipid-soluble molecules diff se thro diffuse throw cell membrane receptor is intracellular female sex hormone Steroid hormone Synthesis All steroid hormones are produced via cholesterol 2 Types of Receptors Receptors • surface receptors – bind peptides & catecholamines – at cell membrane • nuclear receptors – bind thyroid & steroid hormones – inside the cell Surface Receptors Receptors • allll cells ll maybe b exposed d tto hormones via circulation peptides p p & catecholamines ion channel • only l cells ll with ith receptors t for hormone can respond • extracellular chemical (hormone) binds to surface receptor • receptor activation alters – channel function – second-messenger systems enzyme change g in ion flow (e.g. Na, Ca, K, Cl) Increased product signal (eg cAMP) Nuclear Receptors Receptors • steroid receptors bind steroid hormone • hormone-receptor hormone receptor complex becomes a transcription factor (alters gene transcription)) • each steroid receptor binds a unique i DNA sequence (response element within an enhancer region) g ) • this alters the rate of transcription thyroid y & steroid hormones plasma protein carrier oestrogen oestrogen receptor protein synthesis mRNA transcription trans loca tion Surface Receptor Structure Receptors • receptor domains • ligand binding domain (LBD) • 7 transmembrane domains (TMDs) • G-protein coupled • mechanism • • LBD TMDs peptide hormone binds to receptors on the surface of the cell • activates G-protein • induces intracellular signals Neuropeptide Examples: Prolactin, Adrenocorticotrophic hormone (ACTH), Antidiuretic hormone (vasopressin), Oxytocin, Insulin, Somatostatin G-prot PLC AC cAMP IP3 DAG PKA Ca2+ PKC Nuclear Receptor Structure Receptors • receptor domains • Hormone/Ligand binding domain (LBD) • DNA binding domain binds steroid response element (SRE). • Nuclear Localization Signal (NLS) covered by heat shock proteins (HSP) LBD NLS e.g. glucocorticoid receptor HSP SRE-BD • mechanism • binding of hormone induces detaches HSP; uncovers NLS • receptor+hormone enters nucleus • • acts as a transcription factor Examples: E l E Estrogen, t Glucocorticoid Gl ti id (Cortisol), (C ti l) Mineralocorticoid (Aldosterone), Progesterone, Androgen (Testosterone) transcription SRE nucleus Receptor Regulation Receptors • target cell may be unresponsive due to lack of receptors t (physiological, ( h i l i l genetic, ti di disease)) • one hormone can influence activity of another hormone b regulation by l ti off it its receptor: t Permissiveness – one hormone is required for another hormone to work Synergism – actions of several hormones are complimentary – combined effect is greater than sum of separate effects Antagonism – one hormone inhibits another hormone’s receptors – reduces effectiveness of second hormone Summary so far Summary Four types of chemical signals 1) A Autocrine/Paracrine t i /P i 2) Neurotransmitter 3) Neurohormones 4) Hormones Four types of hormones 1) Peptide hormones 2) Catecholamines 3) Thyroid hormone 4) St Steroid id h hormones Types of receptors 1) Extracellular 2) Intracellular ? The endocrine system Endocrine System Endocrine System Overall functions – – – – – – – regulate organic metabolism controls t l water t and d electrolyte l t l t b balance l induces adaptive changes to cope with stress promotes t growth th and d development d l t controls reproduction regulates red blood cell production controls circulation, digestion, absorption of food Endocrine Hormone Concentrations Endocrine System • plasma l conc. off hormones h controlled t ll d b by rate t of: f – secretion – metabolism and excretion – binding to plasma proteins • secretory output of endocrine cells controlled by – neurall input i – other hormones Neuro-Endocrine System Endocrine System nervous and endocrine systems co-regulate many physiological functions study of this is called Neuro-Endocrinology Neuro-Endocrinology studies how the brain regulates g Pituitary y hormone secretion Neuro-Endocrine cells Classification Neuroendocrine cells release neurohormones Found in, for example: • • • • • • • • adrenal medulla thyroid islet of Langerhangs pituitary p y cells renin-secreting cells gastro-intestinal tract pancreas lower respiratory tract Primary & Secondary Endocrine Glands Endocrine System Primary P i Endocrine E d i Organs O – discrete organs – main function is endocrine hormone release – pituitary, thyroid, parathyroid, adrenal and pineal i l glands l d Secondary S d Endocrine E d i Organs O – dispersed in organs – have other major functions – heart, kidney, liver, etc. Endocrine Glands Endocrine System – derived from epithelial tissue – composed of clumps of secretory cells – surrounded by capillaries (fenestrated) – exocrine glands have ducts – endocrine glands have no duct system Exocrine Glands: Classify by Morphology Exocrine System Simple Types Endocrine glands ─ secret hormones into bl d t bloodstream Exocrine glands ─ discharge products via duct tubular large intestine acinar urethra branched tubular stomach branched acinar Compound Types Exocrine Types ─ simple / compound tubular acinar coiled tubular sweat glands Exocrine Glands: Classify by Secretion Exocrine System Merocrine (eccrine) Secretion • exocytosis • most common type of secretion Apocrine p Secretion • membrane-bound vesicles • example: breasts, sweat glands Holocrine Secretion • rupture off secretory cells ll • example: sebaceous glands Feedback Endocrine System ─ endocrine glands secretion triggered by ─ hormones ─ neurotransmitters ─ metabolic factors ─ two types of feedback loops ─ long-loop ─ short-loop ─ feedback can be ─ excitatory y ─ inhibitory Feedback Mechanisms Endocrine System Gland 1 - Positive Feedback e.g. Hormone 3 activates Gland 2 Hormone 1 Gland 2 Negative Feedback Hormone 2 e.g. g Hormone 3 inhibits Gland 1 Gland 3 Hormone 3 + Trophic Hormones Endocrine System • ttrophic hi hormones h regulate l t secretion ti other hormones (either releasing or inhibitory) • example l – thyroid-stimulating hormone (TSH) – secreted from anterior pituitary – stimulates thyroid hormone secretion from thyroid gland – maintains structural integrity of thyroid gland Anterior pituitary Thyroid stimulating hormone (TSH) Thyroid gland Thyroid Hormone (T3.T4) Disease: Hyposecretion Endocrine System Primary hyposecretion • due to abnormality within gland • causes – – – – – – – genetic dietary (eg lack of iodine) chemical or toxic immunologic (autoimmune diseases) cancer surgery (removal / Iatrogenic) idiopathic (unknown) Secondary hyposecretion • deficiency of tropic hormone Disease: Hypersecretion Endocrine System • Causes – tumours continuously secrete hormone – immune factors • Primary hypersecretion – too much hormone secreted due to abnormality within gland • Secondary hypersecretion – excessive stimulation of g gland causes oversecretion Summary Summary 4 types of chemical signals 1) Autocrine/Paracrine 2) Neurotransmitter 3) Neurohormones 4) Hormones 4 types of hormones 1) Peptide hormones 2) Catecholamines 3) Thyroid hormone 4) Steroid hormones 2 Types of receptors 1) Extracellular 2)) Intracellular Feedback and Tropic hormones 1) Long and short loops 2) Positive and negative 2. Types of glands 1) Primary 2) Secondary Causes and types of 1) h hyposecretion ti 2) hypersecretion