Exam 4 Material
Exam 4 Material PHCL2600
Popular in Funct Anat and Pathophysiol I
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Date Created: 11/22/15
Lecture 1 0 Comparison of Nervous and Endocrine Systems Characteristics Nervous System Endocrine System Mediator molecules Site of mediator action Types of target cells Time to onset of action Duration of action Neurotransmitter released locally Hormones release into the blood circulation At synapse close to the release site Binds to receptors in post synaptic membrane Usually far from site of release Binds to receptors on or in target cells organ or tissue Muscle cells gland cells other neurons Cells throughout the body Within milliseconds Seconds to hours or days Generally brief action milliseconds Generally long action sec to days o The nervous and endocrine systems coordinate all body systems 0 Endocrine System 0 Consists of and containing hormonesecreting cells 0 I Pituitary thyroid adrenal parathyroid and pineal glands o I Hypothalamus thymus pancreas ovaries testes kidneys stomach liver small intestine skin heart adipose tissue and placenta o Endocrine System 0 Controls body activities 0 Function is mediated by molecules called 39 Controls volume control metabolism muscle contraction immune activities growth and development and reproduction o Slower responses effects last longer and broader in uence 0 Hormones o Body s chemical o by cells into the interstitial uid tissue uid and diffuse into the 0 Act 0n o In target tissues hormones bind to specific proteins called o Hormone Concentrations 0 Effects depend on the hormone concentration 0 Types 0 Normal range that produces normal response 0 Small amounts 9 nanomolar to picomolar o Abnormally high or low concentrations 0 Can elicit different responses to normal 39 0 Concentration When a hormone is taken as a drug or medication 0 Exaggerated or noncharacteristic effects 0 Possible adverse side effects Hormone Types 0 Two types 9 and 0 Most hormones are circulating hormones Circulating Hormones o Secreted into o Carried to distant 0 They bind to in target cells 0 They are inactivated by the liver and excreted by the kidney 0 thyroid hormones I Produced and secreted by the thyroid gland I They act on bones growth neurons and other target tissues Local Hormones Autocrines o Secreted into the I They do not enter the blood 0 Hormones act on the that secretes them I Short or no distance from the release site to the target cell 0 Cytokine interleukin1 I Released by monocytes and act on monocytes Local Hormones Paracrines o Secreted into the I They do not enter the blood 0 Act on neighboring cells 9 Diffuse short distance 0 Testosterone I Released from the testes I Acts on adjacent seminiferous tubules to stimulate spermatogenesis Chemical Classes of Hormones o The two classes 0 Classification is based on chemical structure 0 Classification I Watersoluble hormones o Amine 0 Peptideprotein 0 Eicosanoid I Lipidsoluble hormones 0 Steroid 0 Thyroid o Nitric oxide NO 0 WaterSoluble Hormones o Amine hormones I Synthesized by modification of certain amino acids I Examples 0 Norepinephrine epinephrine and dopamine from tyrosine 0 Histamine from histidine 0 Serotonin from tryptophane o Peptideprotein hormones I Amino acid polymers 0 Peptide lt 100 aa 0 Protein gt 100 aa I Examples 0 Oxytocin insulin growth hormone o Stored in secretory vesicles granules inside the cells 0 Stimulus of the cells cause their release I Bind to receptors on the surface of target cells 0 WaterSoluble Hormones o I Derived from fatty acid Arachidonic Acid I Local hormones and may also act as circulating hormones I Not Stored 0 Synthesized rapidly as needed 0 In response to stimuli I Inactive quickly near site of synthesis 0 I Prostaglandins and leukotrienes 0 In ammation 0 WaterSoluble Hormones Transport and Excretion o Free in plasma I Quickly broken down by enzymes or are taken up by tissues I Regulate activities With a rapid onset and a short duration 0 I Hormones are metabolized in liver and excreted by the kidneys o LipidSoluble Hormones o Stimulus causes synthesis and secretion into the blood I Bind to receptors in the cytoplasm or nucleus of the cell o I Synthesized from 39 0 Testosterone aldosterone cortisol estrogen o I Synthesized by attaching I T3 triiodothyrosine and T4 thyroxine o LipidSoluble Hormones Transport and Excretion o I They circulate bound to 0 TP makes them water soluble 0 Not quickly removed from the blood 0 Produce a prolonged effect 0 I Kidneys or liver Lecture 2 0 Carrier Proteins for Lipid Soluble Hormones 0 General carrier proteins I Albumin 0 Steroids 0 Some thyroid hormones I Transthyretin o Thyroid hormones 0 Some steroids 0 Specific carrier proteins I Cortisol binding globulin CBG 0 Cortisol and aldosterone I Thyroxine binding globulin TBG o Thyroid hormones I Sex steroid binding globulin TEBG 0 Testosterone and estradiol 0 They require carrier proteins to make them soluble 0 Control of Hormone Secretion o I Signals from nervous system I Chemical changes of molecules in the blood I Other hormones o I Negative feedback 9 most common I Positive feedback 0 Control of Hormone Secretion o 0 Most endocrine glands under 0 Cells can sense the magnitude of the biological effect produced by the hormone and decrease response 0 Based on magnitude of the effect produced by the hormone cell can decrease response 0 hypothalamuspituitaryorgan axis 0 Control of Hormone Secretion o I Less common 0 I Increases production and release of oxytocin to o Enhance milk production and release 0 Enhance contractions during childbirth Hormone Activity 0 Hormones affect only specific target tissues 0 Only target tissues or cells With a receptor for a specific hormone respond to the hormone Response depends on both hormone and target cell 0 Target cells respond differently to the same hormone I Hormonal effects vary Hormone Activity Receptor 0 o Hormone locks onto a specific receptor 0 Binding of hormone to the receptor unlock the cell s response producing an effect Regulation of Hormone Effects 0 Downstream effect determined by I Number of receptors present I Amount of hormone secreted o Receptors are constantly synthesized and broken down I Downregulation I Upregulation I Increase in hormone leads to decrease in number of receptors I Target cell is less sensitive to hormone O I Increase in hormone leads to increase in number of receptors I Target cell is sensitive to low concentrations of hormone o Hormone binds to a receptor on a target cell 0 Watersoluble hormones bind to receptors on the plasma membrane 0 Lipidsoluble hormones bind to receptors inside target cells I Cytoplasmic or nuclear 0 Surface Receptors for I Single transmembrane protein I Membrane bound protein I 7transmembrane protein G proteincoupled receptor 0 Hormone binds to receptor 0 Leads to I Molecular Response I Cellular Response I Tissue Response o Membranebound receptors I Receptors alter the activity of G proteins 0 Open or close ion channels and activate existing enzymes 0 Cell Response I Receptors alter the activity of intracellular enzymes 0 Activate existing enzymes 0 Cell Response 0 Intracellular receptors I Activate genes 0 Synthesize new proteins or enzymes 0 Cell Response 0 produce responses through the action of I o protein is activated by G proteins 0 Effector produces a Family of membrane bound proteins found adjacent to GPCR Can be stimulatory S or inhibitory i They contain GTPase activity that hydrolyzes GTP Guanosine triphosphate G proteins consist of three subunits heterotrimeric I Alpha 0t Beta B and Gamma y Family of membrane bound proteins found adjacent to GPCR o o consist of heterotrimeric I Alpha 0t Beta B and Gamma y subunits 0 Alpha 0t can be stimulatory Gs inhibitory G1 Gq and G 0 They contain GTPase activity that hydrolyzes GTP guanosine triphosphate O O O O G proteins are present in two states I Active and inactive o In the inactive state I ocBy subunits form a I is bound to the OL subunit I Trimeric complex 0 Ligand binding stimulates the exchange of GDP for GTP 0t subunit dissociates from By subunits Dissociated subunits activate effect GTPase activity hydrolyses GTP G protein goes back to inactive site 0000 0 Three effector systems Effector Second Messenger Adenylate cyclase CAMP Phospholipase C Inositol phosphate Ion channels Ions cAMP cyclic adenosine monophosphate o binds to the receptor and activates a Gs o low concentration of hormone can produce large effect downstream 0 One molecule of hormone interacts With receptor activating one adenylate or adenylyl cyclase Which creates 100 cAMPs o cAMP activates 100 protein kinases o Kinases can phosphorylate 1000s of proteins 0 Inactivation occurs by the action of the enzyme I cAMP is inactivated to AMP I Phosphodiesterase clips the phosphodiester bond Interaction With a stimulatory G protein Gs activates AC Interaction With an inhibitory G protein Gi inhibits AC Inhibition occurs mainly by blocking AC activation adrenergic receptors OOOO Lecture 3 O o A hormone may bind to various types of receptors 0 Epinephrine I Binds to B2 receptors in smooth muscle cells 9 dilation of blood vessels I Binds to on receptors and causes Ca2 movement into cells 9 muscle constriction 9 blood vessel contraction 0 Not a big problem due to receptor distribution I B receptors predominate in skeletal muscle and liver I OL receptors predominate in the viscera and smooth muscles The effector is I Three messenger molecules are produced 0 Diacylglycerol DAG 0 Inositol triphosphate 1P3 0 Ca2 ion o G protein is a Gq type 9 activation of e PLC originates and from the inner membrane 9 uses as second messengers o activates from endoplasmic reticulum o DAG and Ca2 activates PKC resulting in protein phosphorylation I Binding of 0t subunitGTP opens the Ca2 channel I Increase in intracellular Ca2 and release of more Ca2 from ER I Ca2 combines With calmodulin Ca2 binding protein and activates protein kinases calmodulindependent kinases O I Binding of By subunits opens the inward rectifier K channel I K leaves the cell I Hyperpolarization of cells 9 effect of acetylcholine o G proteins I ocsubunit family 0 Gs Gi Gq I By subunits 0 Different B and y subunits o Receptors I Types I Location 0 Effector Systems I Adenylate cyclase I Phospholipase C I Ion channels o Ligand is a molecule that binds to a receptor no only GPCR I Hormones Insulin I Neurotransmitters acetylcholine I Drugs can be more selective e I Agonist positive effect I Antagonist negative effect I Partial Antagonist 12 effect 0 I Relative numbers of receptors I Types of receptors 0 Receptors With positive or negative effects 0 Tissue type 0 These pathways are not only for GPCR o receptor protein goes into the cell I receptor protein is metabolized broken down in the cell I receptor protein is placed back into the membrane 0 o Ligandreceptor complex goes inside the cell by 0 Receptor and ligand are internalized in vesicles called o In recycling the receptor goes back to the plasma membrane to O o Ligandreceptor 0 Receptor and ligand are delivered to for degradation into smaller units 0 Degradation decrease of the number of receptors on the plasma membrane o Kinase domain is in the cytoplasmic region of the receptor 0 undergoes a forming dimers 0 Activation of the 9 autophosphorylation on tyrosine o The kinase activity in the activated receptor phosphorylates intracellular targets enzymes 9 activation or inactivation of target o Lipidsoluble hormones e g steroids bind to cytoplasmic intracellular or nuclear receptors 0 Cytoplasmic glucocorticoid and nuclear estrogen T3 T4 Lecture 4 0 Also called 0 Located at the base of the brain I In a pocket of the sphenoid bone sella turcica just below the hypothalamus 0 Attached to the hypothalamus through the infundibulum or pituitary stalk o It is composed of two regions I or adenohypophysis I or neurohypophysis 0 These regions are anatomically and functionally different o It has three lobes 39 9 Upper lobe 0 It surrounds the infundibulum 9 Intermediate lobe 0 Minimal function in adult humans 0 Releases melanocyte stimulating hormone MSH in some species I 9 Anterior lobe 0 Larger portion 0 Collection of axons from the hypothalamus 0 Part of the hypothalamus 39 0 Contains nerve tracts 39 0 Also called the neural lobe or posterior lobe o Neuronal and vascular connection I Hypophyseal HypothalamoHypophyseal tract 0 Hypothalamus and posterior pituitary connection I Hypophyseal HypothalamoHypophyseal portal system 0 Hypothalamus and anterior pituitary connection o 0 Vascular connections between the hypothalamus and the anterior pituitary o Plexus is a capillary network 0 Anterior hypophyseal veins drain the blood containing hormones into the circulation Hypothalamic hormones Anterior Pituitary hormones CRH T corticotropin releasing hormone ACTH adrenocorticotropic hormone MSH melanocyte stimulating hormone GRH T growth releasing hormone GIH 14 growth inhibiting hormone GH growth hormone TRH T thyrotropin releasing hormone TSH thyroid stimulating hormone GnRH T gonadotropin releasing hormone LH 1uteinizing hormone FSH follicle stimulating hormone PRH T prolactin releasing hormone PIH Jr prolactin inhibiting hormone Pr prolactin Stimulatory T Inhibitory T Cell Type Hormone Somatotropes Growth hormone Corticotropes ACTH amp MSH Thyrotropes Thyroid stimulating hormone Lactotropes Prolactin Gonadotropes Follicle stimulating hormone Luteinizing hormone o types of anterior pituitary 0 Cell synthesize and secrete o Hormones act on other endocrine tissues or systems I Most hormones released from the anterior pituitary are o Tropic hormones stimulate the release of other hormones in a receptormediated and tissue specific manner 0I I By hypothalamic releasing hormones I Levels of secreted hormones from the pituitary andor target organ 0 Stimulatory or inhibitory 0 Can occur at Target Organs Hypothalamus or the Pituitary o ACTH corticotropin is synthesized and secreted by corticotrophs o ACTH is a polypeptide tropic hormone o Often produced with CRH in response to biological stress 0 ACTH stimulates glucocorticoid mainly cortisol secretion by adrenal gland 0 GH is a of about 190 amino acids 0 Hypothalamus releases GHRH that stimulates somatotrophs to produce and secrete GH liver muscle bone and adipose tissue 0 GH has different effects in these tissues I GH stimulates growth in most tissues and is a regulator of metabolism 0 GH binds to its receptor on targets cells in target tissues o Somatomedins 9 hormones that promote cell growth and diVision in response to stimulation by growth hormone Lecture 5 o o Mediated by somatomedins also known as insulinlike growth factors IGFs secreted by the liver step 2 0 GH activates production of somatomedins in liver 0 IGFs act on target cells in target tissues I Growth promoting effects of GH 0 IGF receptors o 0 GH promotes the production of two somatomedins in liver I Insulin like growth factor I o Acts on bone I Insulin like growth factor II o Acts on organs and tissues 0 Somatomedins promote cell growth and division in response to GH 0 GH binding promotes dimerization bringing two receptors together 0 Dimerization is important to recruit tyrosine kinases which phosphorylate the receptor 0 There is phosphorylation and translocation of proteins to the nucleus I Activation of gene transcription in the nucleus GH is released in burst every few hours T Fatty acids and L amino acids in the blood 9 Inhibition of GH secretion secretions is by and released from the Regulation stress exercise nutrition sleep and GH itself 0 O O O 0 Check glucose effects and regulation in Fig 187 for the exam o stimulates GH synthesis and secretion 0 or GHIH inhibits GH release 0 hunger hormoneO binds to receptors on somatotrophs 9 stimulates secretion of GH I High blood levels of IGFI L secretion of GH 0 By directly suppressing somatotrophs and by stimulating SS release from they hypothalamus O I GH inhibits GHRH secetion I A direct inhibitory effect on GH secretion from somatotropes somatotrophs o 1 5000 I No definite cause 9 problems arising in the pituitary gland I 9 L growth hormone release I Growth during childhood is very slow or delayed 9 leads to a proportionate little person less than 4 feet 10 inches I GH and GHRH injections 0 I Normal production of growth hormone Problem is a I biosynthetic IGFI 0 Condition characterized by excessive height growth Rare I secretion the end of adolescence 0 Before the bone growth plates have closed 0 I Remove pituitary tumor O I Somatostatin analogs 9 L GH release o It occurs as a result of excess GH o Enlargement and elongation of the bones of the face jaw cheeks and hands 0 Enlargement of soft tissue of liver heart and kidneys I Hyperglycemia and peripheral neuropathy incurred because of nerve entrapment by excessive bone growth remove tumor and use drugs that inhibit GH release very rare features of acromegaly with normal GH levels Lecture 6 They are They are synthesized and released by gonadotrophs in anterior pituitary They are controlled by hypothalamic ganodotropinreleasing hormone 0000 They are involved in stimulating gonads testis and ovaries I Control the production of male hormones and sperm I In female production of mature egg effect on uterus and production of estrogen and progesterone 0 Essential for reproduction o Stimulates breast growth and development of the mammary glands o Stimulates milk production o Prolactin is o Directly target the end organ 0 Regulatory hormones o Prolactin releasing factor PRF 9 T during pregnancy 0 Prolactininhibiting hormones PIH or dopamine 0 Synthesis and secretion of thyroid hormones by the thyroid gland 0 Levels of thyroid hormones are important for regulation 0 There is not a thyrotropininhibiting hormone o Posterior pituitary consists of unmyelinated axons of hypothalamic neurons 0 0 two hormones made in the hypothalamus o Hormones are transported along o The tract connects the hypothalamus and the posterior pituitary 0 Cell bodies of neurosecretory cells neurons are in two I Paraventricular PVN nucleus I Supraoptic SON nucleus 0 Hormone is synthesized in the soma or cell body I A transports one type of hormone o Hormone is into vesicles and towards the axon terminal 0 Hormone is in vesicles at the axon terminal and by o Hormones are released into the capillary plexus of the infundibulum I Blood supplied by the drains into the capillary plexus o Hormones from the plexus pass into the which carry blood to the general circulation o Stimuli Within the nervous system stimulates hypothalamic neurons to either increase or decrease their action potential frequency 0 Action potentials are carried by axons of the hypothalamic neurons through the hypothalmohypophyseal tract to the posterior pituitary The axons of neurons store hormones in the posterior pituitary o In the posterior pituitary gland action potentials cause the release of hormones from axon terminals into the circulatory system 0 The hormones pass through the circulatory system and in uence the activity of their target tissues 0 Two polypeptide hormones synthesized in the nuclei 0 I Synthesized in cell bodies in the supraoptic nucleus I Synthesized in the paraventricular nucleus o peptide hormone I Cyclic nonapeptide 9 aa s disulfide bridge at cysteines I Arginine vasopressin amino acid sequence 0 CystyrpheglnasncysproI glyNH2 o 9 It promotes water retention 0 I 9 water retention 9 L urine volume I 9 L water loss by perspiration I 9 constriction o ADH binds to V2 vasopressin receptor and activates o T cAMP and activation of PKA o T Synthesis and membrane insertion of Aquaporin 2 or water channels I T Number of channels I T Channel activity 0 Water moves through aquaporin channels I Contain smooth muscle cells O I ADH causes vasoconstriction 0 T Vascular resistance and blood pressure I This action is mediated by V1 receptors GPRC phospholipase C on vascular smooth muscle cells I L Number of surface sweat glands I L Water lost by perspiration 0 Two types of receptors involved in maintaining water balance 39 o In the hypothalamus 39 o Aortic arch and carotid sinus O O O O Sensory receptors Located in the hypothalamus near the supraoptic nucleus Respond to changes in plasma concentration Na 9 osmolarity 00000 O O Sensory receptors Located in the blood vessels e g aorta and carotid arteries Respond to changes in blood pressure 9 stretching of the arterial wall T 9 T blood pressure 9 T stretch 9 They send messages to the CNS to increase or decrease peripheral resistance and cardiac output High blood osmotic pressure stimulates hypothalamic osmoreceptors Osmoreceptors activate neurosecretory cells that synthesize and release ADH Nerve impulses liberate ADH from axon terminals in posterior pituitary into blood stream Kidneys retain more water which decreases urine output sudoiferous sweat glands decrease water loss by perspiration from skin arterioles constrict which increases blood pressure Los blood osmotic pressure inhibits hypothalamic osmoreceptors Inhibition of osmoreceptors reduces or stops ADH secretion 0 0 Pain emotions stress nausea I Increase in vasopressin release Ethanol I L Vasopressin secretion diuretic o o most common I Decreased producing or secretion of ADH I Damage to pituitary gland or hypothalamus o I Synthetic ADH 9 Desmopressin given by injection nasal spray or pill I In mild cases treatment is increased water intake 0 I Excretion of large volumes of urine I Thirst I Dehydration o I Defect in ADH receptors in kidneys Lecture 7 o Synthesized in supraoptic nucleus 0 I First polypeptide hormone to be sequenced and synthesized in 1953 I Oxytocin OT is a cyclic peptide hormone containing 9 amino acids I Differs from vasopressin 9 Leu instead of Arg 0 Cystyrpheglnasncyspro glyNH2 O I During and after delivery of a baby 9 two target tissues 0 Breast 0 Uterus o Oxytocin Receptor is a G proteincoupled receptor 0 Receptor activates PLC producing 1P3 diacylglycerol and Ca2 0 Receptor undergoes downregulation by endocytosis 0 Major site of action in women I Uterus enhances muscle contraction during delivery 0 Pitocin oxytocin injection 0 Laborinducing drug I Breast stimulated milk ejection letdown re ex following delivery 0 Milk goes into subalveolar sinuses from where it can be excreted via the nipple 0 Suggested activity in nonpregnant women and men I Increases our sensitivity to touch and encourages grooming and cuddling in both sexes I Regulation of emotional empathy I Sexual arousal O 0 Released during lactation to stimulate milk ejection Sensory receptors recognize the baby s sucking re ex and a signal is sent to the hypothalamus I Production of oxytocin Removal of the prolactin inhibition in the anterior pituitary T Prolactin and oxytocin producing milk secretion and ejection O 0 0 During child birth parturition it facilitates birth process I T Oxytocin during labor O O I OT stimulates smooth muscle contraction in the wall of the uterus I Estrogen secretion induces an T in oxytocin receptors in uterus There is a positive feedback regulatory mechanism Contractions start slow and increase in number and intensity during the process 00000 The largest endocrine gland Located in the anterior neck and inferior to larynx It wraps around the trachea Two lobes left and right connected by an isthmus median tissue mass Covered by fibrous connective tissue highly vascularized O Thyroid Follicle I Follicular cells surround a central cavity I Cavity is filled with colloid C cells or parafollicular cells produce calcitonin Follicular cells produce the glycoprotein thyro globulin I Cells secrete thyroid hormones Production of thyroid hormones and the hormone calcitonin calcium homeostasis O Consist of two related iodinecontaining compounds 39 o It has two tyrosines with three atoms of iodine 90 39 o It has two tyrosines with four atoms of iodine 10 O O 0 Synthesis is done in the follicles Needs amino acids for hormone synthesis I Thyroglobulin provides tyrosine residues 0 Large glycoprotein made in the follicle cell 9 it contains 140 tyrosines 12 is necessary in the diet I Requirement is 150 mgday I Consumed amounts vary but usually is around 500 mgml O O O Thyroid gland is the only gland that stores hormones in large quantities 100day supply Several steps are involved in the synthesis of thyroid hormones O I Synthesized in the endoplasmic reticulum ER in follicle cells I Modified in the Gogli 9 glycoprotein I Packed in secretory vesicles I Vesicles discharge thyroglobulin into the lumen of follicle by exocytosis 0 I I2 in diet is absorbed and to iodide ion 139 in the gut 9 absorption I I39 is from the blood into the cytoplasm of follicle cells Transporter moves iodide and Na into the cells Iodide is highly concentrated in the thyroid gland I Iodide is transported and released into the lumen of the follicle I Iodide I39 is oxidized to iodine I2 by Thyroid Peroxidase Thyroid Peroxidase is an enzyme present in the colloid lumen I Iodine is covalently linked With tyrosine residues in thyroglobulin 0 Mediated by thyroid peroxidase I Formation of single T1 monoiodotyrosine or doubleiodinated T2 diiodotyrosine species of tyrosine 0 I Peroxidase combines MIT and DIT residues to generate T4 or T3 I two one T1 and aT2 0 T3 and T4 are accumulated in colloid on the surface of thyroid cells 0 Some MIT and DIT residues do not get coupled I TGB With T3 and T4 is brought into the cells by pinocytosis Liberation of T3 and T4 from thyroglobulin o Lysosomal enzymes break down thyroglobulin releasing T3 and T4 0 MIT and DIT are also released I T3 and T4 lipidsoluble diffuse into interstitial uid and then into the blood 0 T4 is secreted in larger amounts than T3 o Iodine from MIT and DIT is salvaged and transported back into the cells as I39 0 T3 and T4 are bound to proteins I Thyroidbinding globulins TGBs o Bind about 70 75 hormones I Transthyretin thyroidbinding prealbumin TBPA and albumin 0 Binds most of the remaining thyroid hormones 0 Binding Capacity T4 I Albumin gt TBPA gt TBG 0 Binding Affinity T4 I TBG gt TBPA and albumin 0 Free hormones are active 004 of plasma T4 and 04 plasma T3 0 Larger amounts of T4 than T3 are released 0 T3 is more potent than T4 0 T3 has faster onset and shorter duration of action 0 main pathway for peripheral metabolism I Deiodinases D1 D2 amp D3 0 Enzymes 9 different tissue distribution I D1 and D2 maintain the formation of T3 from T4 I D3 9 inactivating pathway to rT3 0 Reverse T3 is not active 0 I Liver major site of nondeiodinated degradation of TH I Conjugation with glucuronic and sulfuric acid I Excretion in bile Thyroid Hormone Regulation 0 Thyroidreleasing hormone TRH I Hypothalamic product 0 Thyroidstimulating hormone TSH I Released by anterior pituitary in response to TRH secretion 9 nuclear receptors I Diagnostic test 9 thyroid function 0 Negative feedback effects of T3 and T4 to inhibit TRH and TSH secretion 0 Also called TSH or thyrotropin I Peptide hormone of 202 amino acids 0 Composed of two subunits 0t and B I OL subunit also present in other hormones I B subunit is unique 0 ThyroidStimulating Hormone o Acts on membrane bound receptor GPCRs on follicle cells in the thyroid gland I cAMP as second messenger o Stimulates thyroid cells to synthesize and secrete thyroid hormones T3 and T4 o o Hypothalamus I Signals in CNS activate hypothalamus I It releases TRH that activates anterior pituitary I Release of TSH o Thyroid I TSH activates thyroid I Secretions of T3 and T4 I Activation of target tissues o I Elevated levels of thyroid hormones inhibit the release of TSH anterior pituitary and TRH hypothalamus I L Thyroid hormones 0 Liver 0 Muscle 0 Fat Cells Lecture 8 0 Effects I Basal metabolism I Body temperature I Metabolic effects 0 Carbohydrate metabolism 0 Lipid metabolism 0 Protein metabolism I Tissue growth I On catecholamines o Thyroid hormones increase body metabolism I T Rate at which cells use oxygen and food to produce energy 0 I Daily energy expended while at rest I The energy is sufficient only for the functioning of the vital organs metabolic tasks 0 Heart lungs nervous system kidneys liver intestine muscle sex organs and skin I Increased overall BMR in cells results in heat production T body temp and 02 consumption 9 calorigenic effect I T BMR 9 T Metabolism of lipids carbohydrates and proteins I T protein synthesis 9 some enzyme involved in metabolism 0 Increase in the use of glucose 0 T3 and T4 Actions on Lipid Metabolism o L Lipid synthesis oxidation most affected and mobilization I Increase in lipolysis I Degradation of triglycerides TG to produce fatty acids I T Fatty acids in plasma due to T mobilization I T Boxidation of FA I Lipid stores TG and plasma cholesterol are decreased o o Thyroid hormones promote muscle growth and bone development I Control of protein synthesis and degradation 0 Effect is coupled to that of GH and IGFI o Promotes nervous system development and functioning I Neuron growth myelination and synapse development o Promotes normal reproductive system development and function I Need for puberty onset o Deficiency of thyroid hormones during development infancy or childhood causes and o Sympathomimetic Effect I Enhance the action of catecholamines norepinephrine and epinephrine in target tissues T Adrenergic effects 0 I I Stimulate catecholaminemediated lipolysis I Activates hormone sensitive lipase HSL O I Increase heart rate I Increase blood pressure Genomic effects 9 regulation of gene expression TH dissociate from proteins TH enters the cells by diffusion or transport T4 is converted to T3 by deiodinases T3 enters the nucleus to bind the TH receptor T3 has higher affinity for TH receptor than T4 o I Receptor not bound to hormone forms a complex with a repressor OOOOOO I Complex binds to DNA thyroid response elements and represses transcription basal state 0 I Hormonereceptor complex promotes conformation changes in the protein releasing the repression I Activation of transcription