Endocrine SystemHuiping Wang (), PhDDepartment of PhysiologyRm C516, Block C, Research Building, School of MedicineTel: 88208252Email: email@example.com
RECOMMENDED TEXTBOOK: Widmaier EP, Raff H, Strang KT (2006) Vanders Human Physiology: The Mechanisms of Body Function, Tenth Edition. McGraw-Hill. SUPPLEMENTARY READING: Stephan Sanders (2003) Endocrine and Reproductive systems, Second Edition. Mosby. COURSE WEBSITERS: http://www.endocrineweb.com/ http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/index.html http://medical.physiology.uab.edu/cardio.htm http://www.mhhe.com/biosci/ap/foxhumphys/student/olc/index.htm
Endocrine SystemGeneral Principles of Endocrine PhysiologyHypothalamus and pituitary glandThyroid glandEndocrine Regulation of Calcium and Phosphate MetabolismAdrenal glandPancreatic hormones
General Principles of Endocrine Physiology
OutlineEndocrine system and HormoneHormone types Hormone synthesis, storage, release, transport, clearance and action modesCharacteristics of hormonesRegulation of Hormone SecretionMechanisms of hormone action
Endocrine SystemOne of the two major communication systems in the bodyHave much longer delaysLast for much greater lengths of time
Integrate stimuli and responses to changes in external and internal environment
crucial to coordinated functions of highly differentiated cells, tissues and organs
Endocrine gland (ductless) is a group of cells that produce and secret a hormoneEndocrine GlandsHypothalamusPituitary (Anterior and Posterior)Thyroid / ParathyroidEndocrine Pancreas (islets)Adrenal Cortex and MedullaGonad (Ovary and Testis)
Endocrine SystemThe endocrine system broadcasts its hormonal messages to target cells by secretion into blood and extracellular fluid. Like a radio broadcast, it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond.
What is a hormone?Chemical messenger synthesized by specific endocrine cells in response to certain stimuli and secreted into the bloodTravel via the circulation to affect one or more groups of different cells (target cells) to elicit a physiological responseHormones are primarily information transferring molecules
Types of Hormones
TypesAminesSteroidsProtein andpeptidesExampleT4, T3,catecholamineHormones from adrenal cortexand gonadsMost of hormonesinsulin, oxytocin, GH
SynthesisTyrosineCholesterolDNA mRNA Preprohormone -ProhormoneFeaturelipid insolublelipid solublelipid insoluble
NUCLEUS The DNA code is transcribed into mRNA.
RIBOSOMES The mRNA is translated to give instructions for proteins synthesis.
Synthesis of peptide hormones
Typical synthesis of peptide hormonesPreprohormones- larger hormones produced on the ribosomes of the endocrine cellsProhormones- cleavage of preprohormones by proteolytic enzymes in rERProhormones- packaged into secretory vesicles by the Golgi apparatusProhormones- cleaved to give active hormone and pro-fragmentspre-pro-insulin pro-insulin insulin
Synthesis of steroid hormones
Hormone Storage and ReleaseThyroid and steroid hormonesNot stored as secretory granulesTransferring through plasma membraneProtein and catecholamine hormonesStored as secretory granulesReleased by exocytosis
Hormones are not secreted at auniform rateIn a pulsatile pattern
Diurnal (circadian) rhythm:linked to sleep-wake cycles (cortisol, growth hormone)
Be aware of the pulsatile nature and rhythmic pattern of hormone secretion when relating the serum hormone measurements to normal values
Hormones are not secreted at auniform rateRhythmic secretionCyclicoestrogen, progesterone, LH
Modes of ActionEndocrine transmission of a signal from a classic endocrine cell through bloodstream to a distant target cell e.g. testosterone
Neurocrine hormone is released from a neuron down its axon and then travels via the bloodstream to target cell
Paracrine - hormone acts on adjacent cells e.g. histamine released at site of injury to constrict blood vessel walls and stop bleeding
Autocrine hormone is released and acts on the cell that secreted it. e.g. norepinephrine itself inhibits further release by that cell in the adrenal medulla
A secretion may have several sites of action simultaneously
Norepinephrine - Autocrine action causes negative feedback on secretion.
- Simultaneously, endocrine action causes respiration rate to increase, peripheral blood vessels to constrict, etc.
Hormone TransportPeptides and catecholaminewater solubledissolve in bloodcirculate in blood mainly in free form
Steroid and thyroid hormonescirculate in blood mainly bound to plasma proteinsthe free form is biologically activethe greater binding, the longer half-life
Hormone ClearanceThe half-life of a hormone in bloodis the period of time needed for its concentration to be reduced by half.Free: minBinding: mins, hrs, dayse.g. T4 (6 days); Insulin (0.006 days)Hormone concentration in blood is determined bysecretion rateclearance rateWays of Clearancetarget cell uptakemetabolic degradationurinary or biliary excretion
The metabolic fate of a given hormone molecule in the blood
Characteristics of HormonesRegulates rate of reactionDo not initiateVery specificAmplification effectPresent in very small quantitypg/mL ~ g/mL
Characteristics of HormonesInteraction between hormonesSynergistic actionAntagonistic actionPermissive actionHormone A must be present for the full strength of hormone Bs effect.Up-regulation of one hormones receptors by another hormonethe facilitation of the action of one hormone by another
e.g. the ability of TH to permit epinephrine-induced release of fatty acids from adipose tissue cells (TH causes an no. of epinephrine receptors on the cell)
Three types of inputs to endocrine cells that stimulate or inhibit hormone secretion. Regulation of Hormone Secretion
Regulation of Hormone SecretionNegative feedbackMost commonOccurs when a hormone produces a biologic effect that, on attaining sufficient magnitude, inhibits further secretionPositive feedbackLess commonAmplify the initial biological effect of the hormone
Negative FeedbackCharacteristic of control systems in which systems response opposes the original change in the system.Hormone itself feeds back to inhibit its own synthesis.Regulated product (metabolite) feeds back to inhibit hormone synthesis.Important for homeostatic control.Example: Control of blood glucose by insulin
Positive FeedbackCharacteristic of control systems in which an initial disturbance sets off train of events that increases the disturbance even further.Amplifies the deviation from the normal levelsExample: Oxytocin (suckling)Important for amplification of level for action
Mechanisms of hormone actionsHormone action mediated by the specific receptorsMost hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells. A target cell responds to a hormone because it bears receptors for the hormone.
Hormone ReceptorsStructure Recognition domain binds hormone Coupling domain generates signalLocation cell membrane (e.g. for insulin) cytoplasm (for steroids) nucleus (e.g. for thyroid hormone)Receptor capacity exposure to excess hormone down-regulates capacity low hormone concentration up-regulates capacityThe receptor provides link between a specific extracellular hormoneand the activation of a specific signal-transduction system
Two general mechanisms ofhormone actionSecond messengers enzyme activity (rapid, cytosolic effects)
Gene expression - enzymes synthesis (slow, nuclear effects)
Mechanisms of Peptide Hormone ActionG proteinsare GTP-binding proteins couple hormone receptors to adjacent effector molecule have intrinsic GTPase activity have three subunits: , , subunit bound to GDP inactive G protein subunit bound to GTP active G protein the effect can be either stimulatory (Gs) or inhibitory (Gi)Second messengers cAMP second message system IP3 mechanism Ca2+-calmodulin mechanism
Signal transduction pathway involving adenylate cyclase
Cyclic AMP signaling-sequence of eventsThe hormone (1st messenger) binds to the membrane receptor; the membrane receptor changes shape and bind to G protein (GTP-binding protein)
G protein is activated; binds to GTP (Guanosine 5- triphosphate) and release GDP
Activated G protein moves to membrane and binds and activates adenylate cyclase (GTP is hydrolysed by GTPase activity of G protein)
Activated adenylate cyclase converts ATP to cAMP (second messenger) (if inhibited, no catalysed reaction by AC)
cAMP is free to circulate inside the cell; triggers activation of one to several protein kinase molecules; protein kinase phosphorylates many proteins
The phosphorylated proteins may either be activated or inhibited by phosphorylation
Adenylyl cyclase forms cAMP,a second messenger that activates enzymes used in cellular responses. The phosphodiesterase enzymes terminate thesecond messenger cAMP.
The cAMP system rapidly amplifies the responsecapacity of cells: here, one first messenger ledto the formation of one million product molecules. Amplification effectEach protein kinase can catalyse hundreds of reactions
This receptor-G-protein complex