Presentation on theme: "ENDOCRINOLOGY INTRODUCTION"— Presentation transcript:
1 ENDOCRINOLOGY INTRODUCTION SESSION ONEENDOCRINOLOGY INTRODUCTIONDR SYED SHAHID HABIBMBBS FCPS DSDM PGDCRAssociate ProfessorDept. of PhysiologyCollege of Medicine & KKUHKing Saud University
2 At the end of this Session you should be able to: OBJECTIVESAt the end of this Session you should be able to:List the general chemical categories of hormones and give examples of hormones within each category.Explain how different hormones can exert synergistic, permissive, or antagonistic effects.Explain how hormone concentrations in the blood are regulatedDescribe the mechanisms of actions of hormones
4 Two systems control all physiologic processes: THE NERVOUS SYSTEM exerts point-to-point control through nerves, similar to sending messages by conventional telephone. Nervous control is electrical in nature and fast.THE ENDOCRINE SYSTEM broadcasts its hormonal messages to essentially all 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.
5 Endocrinology is the study of hormones, their receptors and the intracellular signalling pathways they invoke
7 HISTORYThe term hormone was used for the first time by E. H Starling in 1905 to describe SecretinThe first hormone to be isolated in pure form was Insulin
8 The term Hormone is derived from Gr. Word orma`ein to excite A chemical substance formed in one organ and carried in the circulation to another organ on which it exerts a stimulating effectBiologically potent and chemically diverse substances secreted by the ductless glands into the general body circulation and affect the target tissues by activating the second messenger system in target tissues
9 COORDINATION OF BODY FUNCTIONS NeuralAcetylcholineEndocrineGrowth HormoneNeuroendocrinGlucagonParacrineGastro Int HormonesAutocrineNor Epinehprine, IGF-1JuxtacrineGrowth Factors
10 INTERCELLULAR COMMUNICATIONS GAP JunctionsSynapticParacrine & AutocrineEndocrineMessage transmissionDirectly from Cell to CellAcross synaptic cleftBy diffusion in interstitial fluidBy circulating body FluidsLocal or GeneralLocalLocally DiffuseGeneralSpecificity depends onAnatomic locationAnatomic location & ReceptorsReceptors
11 H H H H Endocrine Paracrine Juxtacrine Autocrine “Juxtacrine” describes the interaction of a membrane-bound growth factor on one cell with its membraneboundreceptor on an adjacent cell.An important action of GH on the differentiation of progenitor cells is stimulation of the expressionof the IGF-I gene; IGF-I is produced and releasedby these cells. IGF-I exerts an autocrine mitogenic action onthe cells that produced it or a paracrine action on neighboringcells. In response to IGF-I, these cells undergo division,causing the tissue to grow mainly through cell replication.HHAutocrine
12 CLASSIFICATION Chemical Structure Solubility (Water and Lipid Soluble) Peptides and proteinsSteroidsAmino acid derivativesFatty acid derivatives – (Eicosanoids prostaglandins, prostacyclins, leukotrienes and thromboxanes) ??Solubility (Water and Lipid Soluble)Mechanism Of Action
13 Chemical Classification of Hormones 1. Amino acid derivatives:Hormones derived from tyrosine and tryptophan.NE, Epi, T4.2. Polypeptides and proteins:Polypeptides:Chains of < 100 amino acids in length.ADH.Protein hormones:Polypeptide chains with > 100 amino acids.Growth hormone.Glycoproteins
14 Chemical Classification of Hormones (continued) 3. Lipids derived from cholesterol (Steroids).Are water insoluble hormones.Testosterone.Estradiol.Cortisol.Progesterone.
15 POINTS TO REMEMBERAll harmones secreted by Ovaries, testes and adrenal cortex are steroidsAll hormones secreted by adrenal medulla and thyroid are amines except one (Calcitonin, Dopamine [PIH])All Others are peptides and proteins
16 PROPERTIES Half Life Receptors Onset of Action Types of Actions StorageEfficient Regulation
17 Half Life Hormone Half Life Amines 2-3 min T3 0.75 days T4 6.7 days Polypeptides4-40 minProteinsminSteroids4-120 minThe half-life of a hormone—the time required for the plasma concentration of a given amountof the hormone to be reduced to half its reference level—rangesfrom minutes to hours for most hormones
18 TRANSPORTWater Soluble Hormones are transported dissolved in Plasma eg: PeptidesLipid Soluble hormones are reversibly bound to Plasma Proteins (Steroids & Thyroid hormones….thyroid binding globulin, thyroid binding albumin, thyroid binding pre-albumin)Exception catecholamnies 50% free and 50% bound to plasma proteins
29 MECHANISM OF ACTION RECEPTORS INTRACELLULAR SIGNALLING CELL MEMBRANE (Prot, Peptides, Catecholamines)CYTOPLASM (Steroids)NUCLEUS (Thyroid H)INTRACELLULAR SIGNALLINGCHANGE IN MEMBRANE PERMEABILITYACTIVATION OF INTRACELLULAR ENZYMESACTIVATION OF GENES TO PRODUCE NEW PROTEINS1. All steroids (cytoplasm) and amino acid derivatives (Thyroid h in Nucleus) are lipid soluble and havereceptors inside the cell2. All peptides and proteins are water soluble and havereceptors on cell membrane
30 Alters channel permeability Activates second Messenger system ENDOCRINEGLANDHORMONERAlters channel permeabilityActivates second Messenger systemActivation of genesTARGET CELLPHYSIOLOGIC EFFECTS
31 RECEPTORSExtracellular domains (ligand-binding domain) Transmembrane domains are Cytoplasmic or intracellular domains (effector region)
32 RECEPTORS Location of Receptor Classes of Hormones Principle Mechanism of ActionCell surface receptors (plasma membrane)Proteins and peptides, catecholamines and eicosanoidsGeneration of second messengers which alter the activity of other molecules - usually enzymes - within the cellIntracellular receptors (cytoplasm and/or nucleus)Steroids and thyroid hormonesAlter transcriptional activity of responsive genes
33 Inactive c AMP dependant Protein + ATP ADP + Protein PO4 HECFRAdenylCyclaseGs ProteinICFCell’sResponseATPc AMPInactive c AMP dependantProtein KinaseActive c AMP dependantProtein KinaseProtein + ATP ADP + Protein PO4
41 STORAGE, SYNTHESIS, SECRETION Polypeptide and Proteins are stored in Secretory VesiclesSteroid Hormones are usually not storedSYNTHESISSECRETION Bursts, Volleys, Spurts
42 Large inactive protein molecules Endoplasmic Reticulum SYNTHESIS OF PEPTIDESRibosomes on Rough ERPrepro HormonesLarge inactive protein moleculesCleaved inEndoplasmic ReticulumPro HormonesPacked in Golgi App toSecretory VesiclesActive HormonesInactive FragmentsExocytosisActive Hormones
46 CHARACTERISTICSA single endocrine gland may produce multiple hormones (eg: Pituitary)A single hormone may be produced by more than one endocrine gland (Somatostatin by hypoth & Pancreas)A single hormone can have more than one type of target cells and can induce more than one type of effect (Vasopressin)A single target cell may be influenced by more than one hormone (Insulin & Glucagon actions on liver)Same chemical substance can be a hormone and neurotransmitter (eg: Norepinephrine)Organs can be exclusively endocrine or mixed (Pancreas)Some hormones have two names (Somatostatin & GHIH)
48 HORMONE ACTIONS Tropic & Non Tropic Permissive (eg: Thyroid H for GH) Synergism (Potentiating)AdditiveAgonist and AntagonistDown Regulation (Desensitization)Up Regulation (Priming Effect)One hormone must be present in adequate amount for another hormone to exert its actionsMaintenance of the Vascular Response to Norepinephrine.Ex: Glucocorticoids are required for the normal responses of vascularsmooth muscle to the vasoconstrictor action of norepinephrine.NE is much less active on vascular smooth musclein the absence of glucocorticoids and is another example ofthe permissive action of glucocorticoids.
52 At the end of this Session you should be able to: OBJECTIVESAt the end of this Session you should be able to:Describe the functional relationship between the pituitary and the hypothalamus.List the hormones of the anterior pituitary and explain how their secretion is regulated by the hypothalamus.
54 PITUITARY Oval in Shape 8 mm anteroposteriorly 10-13 mm transversely 5 mm height500 mgPituitary gland consist of two lobesAnterior (Adenohypophysis) originates from Rathke’s pouch (pharyngeal epithelium)Posterior (Neurohypophysis) originates from hypothalamus (glial-type cells)
55 Hypothalamus Controls Pituitary Secretion Hypothalamic releasing and inhibitory hormones are conducted to the anterior pituitary through blood vessels called hypothalamic-hypophysial portal vessels.Nerve fibers carry hormones synthesized in the hypothalamus to the posterior pituitary
58 Hormones of the Hypothalamus Thyrotropin-releasing hormone (TRH)Gonadotropin-releasing hormone (GnRH)Growth hormone-releasing hormone (GHRH)Growth hormone-inhibiting hormone (GHIH) also called SomatostatinCorticotropin-releasing hormone (CRH)Prolactin Inhibiting Hormone (PIH) DopamineAntidiuretic hormone (ADH) & Oxytocin are synthesized in hypothalamus and carried by neurosecretary neurons to be stored in post pituitary and released from there.
60 ANTERIOR PITUITARY HORMONES Thyroid Stimulating Hormone (TSH)GonadotropinsFollicle Stimulating Hormone (FSH)FSH in femalesFSH in malesLuteinizing Hormone (LH)LH in femalesLH in malesProlactin (PRL)Growth Hormone (GH)Adrenocorticotropic Hormone (ACTH)PARS INTERMEDIAα β γ-MSH , γ LPHno known effect
61 Hormones-secreting cells of the human anterior pituitary gland 5 Cell TypeHormones Secreted% of TotalStain AffinitySomatotropeGrowth hormone50AcidophlicLactotropeProlactin(10-30)CorticotropeACTH, β-LPH10BasophilicThyrotropeTSH5GonadotropeFSH, LH20ChromophobesThese are cells that have minimal or no hormonal content. may be acidophils or basophils that have degranulatedmay be stem cells that have not yet differentiated into hormone-producing cells.
62 Anterior Pituitary Posterior Pituitary HormoneMajor target organ(s)Major Physiologic EffectsAnterior PituitaryGrowth hormoneLiver, adipose tissuePromotes growth (indirectly), control of protein, lipid and carbohydrate metabolismThyroid-stimulating hormoneThyroid glandStimulates secretion of thyroid hormonesAdrenocorticotropic hormoneAdrenal gland (cortex)Stimulates secretion of glucocorticoidsProlactinMammary glandMilk productionLuteinizing hormoneOvary and testisControl of reproductive functionFollicle-stimulating hormonePosterior PituitaryAntidiuretic hormoneKidney, Blood VesselsConservation of body waterOxytocinStimulates milk ejection and uterine contractions
68 At the end of this Session you should be able to: OBJECTIVESAt the end of this Session you should be able to:Describe the mechanism of action of GHExplain Direct and Indirect effects of Growth HormoneList factors which increase & decrease GH levelsDescribe regulation of GH SecretionDescribe effects of hyper & hyposecretion
69 Growth Hormone (hGH-N) Somatotropin Chromosome 17Source Anterior PituitaryChemistry Protein 191 aahGH-N (75 %)hGH-VMolecular Weight (22 K / 20 K)Half Life 6-20 minDaily Output mg per dayBasal Levels 3 ng/mlTransport Half Dissolved in Plasma and Half Protein Bound
70 MECHANISM OF ACTION?Phospholipase C PathwayJAK STAT Pathway
72 ECF JAK JAK ICF ER Ca++ Phospholipase C PIP2 DAG + IP3 ActiveProtein Kinase CInactiveProtein Kinase CProtein PO ProteinCell’s ResponseCell’s Response
73 Physiologic Effects of Growth Hormone Direct effects are the result of growth hormone binding its receptor on target cells eg. Fats & CarbohydratesIndirect effects are mediated primarily by a insulin-like growth factor-1 (IGF-1) eg. On bones & Proteins
75 GROWTH HORMONE (GH) binding to receptors on the surface of liver cells release insulin-like growthfactor-1(IGF-1; also known as somatomedin)IGF-1 acts onbones, cartilage & proteins for growth
76 (Increased Chondrogenesis and Increased Osteoblastic activity) Long term effectsPromotion of growth: cellular sizes & mitosis tissue growth & organ size(Increased Chondrogenesis and Increased Osteoblastic activity)Short term effectsMetabolic Effects on:1. Carbohydtrates2. Proteins3. Lipids
79 Positive Nitrogen and Phosphorus Balance Increase in lean body mass METABOLIC EFFECTSProtein metabolism:Increased amino acid uptakeIncreased protein synthesis ( transcription & translation)Decreased catabolism of proteinsProtein anabolismPositive Nitrogen and Phosphorus BalanceIncrease in lean body mass
80 Provides Fats as a Major Energy Source METABOLIC EFFECTSFat metabolism:Release fatty acids from adipose tissuue & conversion to acetyl CoA to provide energyStimulate triglyceride breakdown and oxidation in adipocytesProvides Fats as a Major Energy SourceKetogenic effect
81 Conservation of Glucose for Glucose dependant Tissues METABOLIC EFFECTSCarbohydrate metabolism:Anti-insulin activity ( insulin resistance)Enhance hepatic glucose output (gluconeogenesis)Decreases the number of insulin receptorsSupresses uptake of glucose in peripheral tissues like skeletal muscle & fatConservation of Glucose for Glucose dependant TissuesDiabetogenic effect
82 OTHER EFFECTS Increases calcium absorption from GIT Strengthens and increases the mineralization of boneRetention of Na+ and K+Increases muscle massStimulates the growth of all internal organs excluding the brainContributes to the maintenance and function of pancreatic isletsStimulates the immune system
87 Grwoth Periods & Catch-Up Growth PHYSIOLOGY OF GROWTHPHYSICALMENTALGONADALGenetic DeterminationRole of NutritionFreedom from Chronic Diseases & StressHormonal EffectsIGF-1 (Production depends on adequate nutrition)Androgens and EstrogensThyroid HormonesInsulinAdrenocortical HormonesGrwoth Periods & Catch-Up Growth
88 Girls mature earlier than boys and their growth spurt appears earlier than boys Rate of growth in boys and girls from birth to age 20
89 Growth of different tissues at various ages as a percentage of size at age 20
91 GROWTH HORMONE DISORDERS PanhypopituitarismDwarfismLaron dwarfism (GH Normal & IGF-I is markedly reduced)GigantismAcromegalyShort stature may also be caused by mechanisms independent of specific defects in the growth hormone axis. It is characteristic of childhood hypothyroidism (cretinism) and occurs in patients with precocious puberty. It is also part of the syndrome of gonadal dysgenesis seen in patients who have an XO chromosomal pattern instead of an XX or XY pattern (see Chapter 25). Various bone and metabolic diseases also cause stunted growth, and in many cases there is no known cause ("constitutional delayed growth"). Chronic abuse and neglect can also cause dwarfism in children, independent of malnutrition. This condition is known as psychosocial dwarfism or the Kaspar Hauser syndrome, named for the patient with the first reported case. Finally, achondroplasia, the most common form of dwarfism in humans, is characterized by short limbs with a normal trunk. It is an autosomal dominant condition caused by a mutation in the gene that codes for fibroblast growth factor receptor 3 (FGFR3). This member of the fibroblast growth receptor family is normally expressed in cartilage and the brain.
92 DwarfismFailure to growthShort statureMild obesityDelayed puberty
93 Before disappearance of Epiphyseal plates GIANTISMBefore disappearance of Epiphyseal plates
99 Prolactin Source Anterior Pituitary Chemistry Protein 198 aa Effects Prolactin promotes mammary gland development and increases milk productionLactation can be terminated by dopaminergicagonists that reduce PRL or by the discontinuation ofsuckling.
101 PRL levels, which are elevated by the end of gestation, decline by 50% within the first postpartum week and decreaseto near pregestation levels by 6 months. Sucklingelicits a rapid and significant rise in plasma PRL. Theamount released is determined by the intensity and durationof nipple stimulation. The exact mechanism by whichsuckling triggers PRL release is unclear, but the suppressionof dopamine, the major inhibitor of PRL release, andthe stimulation of prolactin-releasing factor(s) have beenconsidered. Lactation can be terminated by dopaminergicagonists that reduce PRL or by the discontinuation ofsuckling. Swollen alveoli can depress milk production byexerting local pressure, resulting in vascular stasis andalveolar regression.