Y khoa, y dược - The endocrine system: Part A

16The Endocrine System: Part AEndocrine System: OverviewActs with the nervous system to coordinate and integrate the activity of body cellsInfluences metabolic activities by means of hormones transported in the blood Responses occur more slowly but tend to last longer than those of the nervous systemEndocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands Endocrine System: OverviewSome organs produce both hormones and exocrine products (e.g., pancreas and gonads)The hypothalamus has both neural and endocrine functions Other tissues and organs that produce hormones include adipose cells, thymus, cells in the walls of the small intestine, stomach, kidneys, and heartFigure 16.1Pineal glandHypothalamusPituitary glandParathyroid glands(on dorsal aspectof thyroid gland)ThymusThyroid glandAdrenal glandsPancreasOvary (female)Testis (male)Chemical MessengersHormones: long-distance chemical signals that travel in the blood or lymphAutocrines: chemicals that exert effects on the same cells that secrete themParacrines: locally acting chemicals that affect cells other than those that secrete themAutocrines and paracrines are local chemical messengers and will not be considered part of the endocrine systemChemistry of HormonesTwo main classes1. Amino acid-based hormones Amines, thyroxine, peptides, and proteins2. SteroidsSynthesized from cholesterolGonadal and adrenocortical hormonesMechanisms of Hormone ActionHormone action on target cellsAlter plasma membrane permeability of membrane potential by opening or closing ion channelsStimulate synthesis of proteins or regulatory molecules Activate or deactivate enzyme systemsInduce secretory activityStimulate mitosisMechanisms of Hormone ActionTwo mechanisms, depending on their chemical natureWater-soluble hormones (all amino acid–based hormones except thyroid hormone)Cannot enter the target cellsAct on plasma membrane receptorsCoupled by G proteins to intracellular second messengers that mediate the target cell’s responseMechanisms of Hormone ActionLipid-soluble hormones (steroid and thyroid hormones)Act on intracellular receptors that directly activate genesPlasma Membrane Receptors and Second-Messenger Systems cAMP signaling mechanismHormone (first messenger) binds to receptorReceptor activates G proteinG protein activates adenylate cyclaseAdenylate cyclase converts ATP to cAMP (second messenger) cAMP activates protein kinasesPlasma Membrane Receptors and Second-Messenger Systems cAMP signaling mechanismActivated kinases phosphorylate various proteins, activating some and inactivating otherscAMP is rapidly degraded by the enzyme phosphodiesteraseIntracellular enzymatic cascades have a huge amplification effectFigure 16.2 Hormone (1st messenger)binds receptor. Receptoractivates Gprotein (GS). G proteinactivatesadenylatecyclase. cAMP acti-vates proteinkinases. Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).ReceptorG protein (GS)Adenylate cyclaseTriggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)Hormones thatact via cAMPmechanisms:EpinephrineACTHFSHLHInactiveprotein kinaseExtracellular fluidCytoplasmActiveproteinkinaseGDPGlucagonPTHTSHCalcitonin12345Figure 16.2, step 1 Hormone (1st messenger)binds receptor.ReceptorHormones thatact via cAMPmechanisms:EpinephrineACTHFSHLHExtracellular fluidCytoplasmGlucagonPTHTSHCalcitonin1Figure 16.2, step 2 Hormone (1st messenger)binds receptor. Receptoractivates Gprotein (GS).ReceptorG protein (GS)Hormones thatact via cAMPmechanisms:EpinephrineACTHFSHLHExtracellular fluidCytoplasmGDPGlucagonPTHTSHCalcitonin12Figure 16.2, step 3 Hormone (1st messenger)binds receptor. Receptoractivates Gprotein (GS). G proteinactivatesadenylatecyclase.ReceptorG protein (GS)Adenylate cyclaseHormones thatact via cAMPmechanisms:EpinephrineACTHFSHLHExtracellular fluidCytoplasmGDPGlucagonPTHTSHCalcitonin123Figure 16.2, step 4 Hormone (1st messenger)binds receptor. Receptoractivates Gprotein (GS). G proteinactivatesadenylatecyclase. Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).ReceptorG protein (GS)Adenylate cyclaseHormones thatact via cAMPmechanisms:EpinephrineACTHFSHLHExtracellular fluidCytoplasmGDPGlucagonPTHTSHCalcitonin1234Figure 16.2, step 5 Hormone (1st messenger)binds receptor. Receptoractivates Gprotein (GS). G proteinactivatesadenylatecyclase. cAMP acti-vates proteinkinases. Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).ReceptorG protein (GS)Adenylate cyclaseTriggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)Hormones thatact via cAMPmechanisms:EpinephrineACTHFSHLHInactiveprotein kinaseExtracellular fluidCytoplasmActiveproteinkinaseGDPGlucagonPTHTSHCalcitonin12345Intracellular Receptors and Direct Gene ActivationSteroid hormones and thyroid hormoneDiffuse into their target cells and bind with intracellular receptorsReceptor-hormone complex enters the nucleus Receptor-hormone complex binds to a specific region of DNAThis prompts DNA transcription to produce mRNAThe mRNA directs protein synthesisFigure 16.3mRNANew proteinDNAHormoneresponseelementsReceptor-hormonecomplexReceptorproteinCytoplasmNucleusExtracellular fluidSteroidhormone The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor. The receptor-hormone complex entersthe nucleus. The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence). Binding initiatestranscription of thegene to mRNA. The mRNA directsprotein synthesis.Plasmamembrane12345Figure 16.3, step 1Receptor-hormonecomplexReceptorproteinCytoplasmNucleusExtracellular fluidSteroidhormone The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor.Plasmamembrane1Figure 16.3, step 2Receptor-hormonecomplexReceptorproteinCytoplasmNucleusExtracellular fluidSteroidhormone The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor. The receptor-hormone complex entersthe nucleus.Plasmamembrane12Figure 16.3, step 3DNAHormoneresponseelementsReceptor-hormonecomplexReceptorproteinCytoplasmNucleusExtracellular fluidSteroidhormone The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor. The receptor-hormone complex entersthe nucleus. The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence).Plasmamembrane123Figure 16.3, step 4mRNADNAHormoneresponseelementsReceptor-hormonecomplexReceptorproteinCytoplasmNucleusExtracellular fluidSteroidhormone The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor. The receptor-hormone complex entersthe nucleus. The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence). Binding initiatestranscription of thegene to mRNA.Plasmamembrane1234Figure 16.3, step 5mRNANew proteinDNAHormoneresponseelementsReceptor-hormonecomplexReceptorproteinCytoplasmNucleusExtracellular fluidSteroidhormone The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor. The receptor-hormone complex entersthe nucleus. The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence). Binding initiatestranscription of thegene to mRNA. The mRNA directsprotein synthesis.Plasmamembrane12345Target Cell SpecificityTarget cells must have specific receptors to which the hormone bindsACTH receptors are only found on certain cells of the adrenal cortexThyroxin receptors are found on nearly all cells of the bodyTarget Cell ActivationTarget cell activation depends on three factorsBlood levels of the hormoneRelative number of receptors on or in the target cellAffinity of binding between receptor and hormoneTarget Cell ActivationHormones influence the number of their receptorsUp-regulation—target cells form more receptors in response to the hormoneDown-regulation—target cells lose receptors in response to the hormoneHormones in the BloodHormones circulate in the blood either free or boundSteroids and thyroid hormone are attached to plasma proteinsAll others circulate without carriersThe concentration of a circulating hormone reflects: Rate of releaseSpeed of inactivation and removal from the bodyHormones in the BloodHormones are removed from the blood byDegrading enzymesKidneysLiver Half-life—the time required for a hormone’s blood level to decrease by halfInteraction of Hormones at Target CellsMultiple hormones may interact in several waysPermissiveness: one hormone cannot exert its effects without another hormone being presentSynergism: more than one hormone produces the same effects on a target cellAntagonism: one or more hormones opposes the action of another hormoneControl of Hormone ReleaseBlood levels of hormonesAre controlled by negative feedback systemsVary only within a narrow desirable rangeHormones are synthesized and released in response toHumoral stimuliNeural stimuliHormonal stimuliHumoral StimuliChanging blood levels of ions and nutrients directly stimulates secretion of hormones Example: Ca2+ in the bloodDeclining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone)PTH causes Ca2+ concentrations to rise and the stimulus is removedFigure 16.4a(a) Humoral StimulusCapillary (lowCa2+ in blood)ParathyroidglandsThyroid gland(posterior view)PTHParathyroidglands1 Capillary blood containslow concentration of Ca2+,which stimulates2 secretion ofparathyroid hormone (PTH)by parathyroid glands*Neural StimuliNerve fibers stimulate hormone releaseSympathetic nervous system fibers stimulate the adrenal medulla to secrete catecholamines Figure 16.4b(b) Neural StimulusCNS (spinal cord)Medulla ofadrenalglandPreganglionicsympatheticfibersCapillary 1 Preganglionic sympatheticfibers stimulate adrenalmedulla cells2 to secrete catechola-mines (epinephrine andnorepinephrine)Hormonal StimuliHormones stimulate other endocrine organs to release their hormones Hypothalamic hormones stimulate the release of most anterior pituitary hormonesAnterior pituitary hormones stimulate targets to secrete still more hormonesHypothalamic-pituitary-target endocrine organ feedback loop: hormones from the final target organs inhibit the release of the anterior pituitary hormonesFigure 16.4c(c) Hormonal StimulusHypothalamusThyroidglandAdrenalcortexGonad(Testis)Pituitarygland1 The hypothalamus secreteshormones that2 stimulatethe anteriorpituitary glandto secretehormonesthat3 stimulate other endocrineglands to secrete hormonesNervous System ModulationThe nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms Example: under severe stress, the hypothalamus and the sympathetic nervous system are activated As a result, body glucose levels rise The Pituitary Gland and HypothalamusThe pituitary gland (hypophysis) has two major lobesPosterior pituitary (lobe):Pituicytes (glial-like supporting cells) and nerve fibersAnterior pituitary (lobe) (adenohypophysis)Glandular tissue Pituitary-Hypothalamic RelationshipsPosterior lobeA downgrowth of hypothalamic neural tissueNeural connection to the hypothalamus (hypothalamic-hypophyseal tract)Nuclei of the hypothalamus synthesize the neurohormones oxytocin and antidiuretic hormone (ADH)Neurohormones are transported to the posterior pituitaryFigure 16.5a1234 Hypothalamicneuronssynthesize oxytocin and ADH. Oxytocin and ADH aretransported along the hypothalamic-hypophyseal tract to the posterior pituitary. Oxytocin and ADH arestored in axon terminals in the posterior pituitary. Oxytocin and ADH are released into the blood when hypothalamic neurons fire.Paraventricularnucleus Supraopticnucleus Optic chiasmaHypothalamusInferiorhypophyseal arteryOxytocinADHInfundibulum (connecting stalk)Hypothalamic-hypophysealtractAxon terminalsPosteriorlobe ofpituitary(a) Relationship between the posterior pituitary and the hypothalamusPituitary-Hypothalamic RelationshipsAnterior Lobe:Originates as an out-pocketing of the oral mucosaHypophyseal portal systemPrimary capillary plexusHypophyseal portal veinsSecondary capillary plexus Carries releasing and inhibiting hormones to the anterior pituitary to regulate hormone secretionFigure 16.5b123 When appropriatelystimulated, hypothalamic neurons secrete releasing and inhibiting hormones into the primary capillary plexus. Hypothalamic hormones travel through the portal veins to the anterior pituitary where they stimulate or inhibit release of hormones from the anterior pituitary. Anterior pituitaryhormones are secreted into the secondary capillary plexus.HypothalamusHypothalamic neuroncell bodiesHypophysealportal systemSuperiorhypophyseal artery (b) Relationship between the anterior pituitary and the hypothalamusAnterior lobeof pituitaryTSH, FSH, LH, ACTH, GH, PRL• Primary capillary plexus• Hypophyseal portal veins• Secondary capillary plexusAnterior Pituitary HormonesGrowth hormone (GH)Thyroid-stimulating hormone (TSH) or thyrotropinAdrenocorticotropic hormone (ACTH)Follicle-stimulating hormone (FSH)Luteinizing hormone (LH)Prolactin (PRL)Anterior Pituitary HormonesAll are proteinsAll except GH activate cyclic AMP second-messenger systems at their targetsTSH, ACTH, FSH, and LH are all tropic hormones (regulate the secretory action of other endocrine glands)Growth Hormone (GH)Produced by somatotrophs Stimulates most cells, but targets bone and skeletal musclePromotes protein synthesis and encourages use of fats for fuelMost effects are mediated indirectly by insulin-like growth factors (IGFs)Growth Hormone (GH)GH release is regulated byGrowth hormone–releasing hormone (GHRH) Growth hormone–inhibiting hormone (GHIH) (somatostatin)Actions of Growth HormoneDirect action of GHStimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factorsMobilizes fats, elevates blood glucose by decreasing glucose uptake and encouraging glycogen breakdown (anti-insulin effect of GH)Homeostatic Imbalances of Growth HormoneHypersecretionIn children results in gigantismIn adults results in acromegalyHyposecretionIn children results in pituitary dwarfismFigure 16.6Growth hormoneFeedbackInhibits GHRH releaseStimulates GHIHreleaseInhibits GH synthesisand releaseAnteriorpituitaryLiver andother tissuesIndirect actions(growth-promoting)Direct actions(metabolic,anti-insulin)Insulin-like growthfactors (IGFs)ExtraskeletalSkeletalFatCarbohydratemetabolismIncreased cartilageformation andskeletal growthIncreased proteinsynthesis, andcell growth andproliferationIncreasedfat breakdownand releaseIncreased bloodglucose and otheranti-insulin effectsEffectsEffectsProduceHypothalamussecretes growthhormone—releasinghormone (GHRH), andsomatostatin (GHIH)Initial stimulusPhysiological responseResultIncreases, stimulatesReduces, inhibitsThyroid-Stimulating Hormone (Thyrotropin)Produced by thyrotrophs of the anterior pituitaryStimulates the normal development and secretory activity of the thyroidThyroid-Stimulating Hormone (Thyrotropin)Regulation of TSH releaseStimulated by thyrotropin-releasing hormone (TRH)Inhibited by rising blood levels of thyroid hormones that act on the pituitary and hypothalamus Figure 16.7HypothalamusAnterior pituitaryThyroid glandThyroidhormonesTSHTRHTarget cellsStimulatesInhibitsAdrenocorticotropic Hormone (Corticotropin)Secreted by corticotrophs of the anterior pituitaryStimulates the adrenal cortex to release corticosteroidsAdrenocorticotropic Hormone (Corticotropin)Regulation of ACTH releaseTriggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythmInternal and external factors such as fever, hypoglycemia, and stressors can alter the release of CRHGonadotropinsFollicle-stimulating hormone (FSH) and luteinizing hormone (LH)Secreted by gonadotrophs of the anterior pituitaryFSH stimulates gamete (egg or sperm) productionLH promotes production of gonadal hormonesAbsent from the blood in prepubertal boys and girlsGonadotropinsRegulation of gonadotropin releaseTriggered by the gonadotropin-releasing hormone (GnRH) during and after pubertySuppressed by gonadal hormones (feedback)Prolactin (PRL)Secreted by lactotrophs of the anterior pituitaryStimulates milk productionProlactin (PRL)Regulation of PRL releasePrimarily controlled by prolactin-inhibiting hormone (PIH) (dopamine)Blood levels rise toward the end of pregnancySuckling stimulates PRH release and promotes continued milk production