Presentation on theme: "PROGRAM KEDOKTERAH HEWAN UNIVERSITAS BRAWIJAYA"— Presentation transcript:
1 PROGRAM KEDOKTERAH HEWAN UNIVERSITAS BRAWIJAYA Hormone ??PROGRAM KEDOKTERAH HEWANUNIVERSITAS BRAWIJAYA
2 Biological function at each level of organization Organism levelOrgan system levelOrgan and Tissue levelsCellular levelMacromolecular levelMolecular level0.2 mm20 µm2 µm200 nm20 nm2 nm0.2 nmAtomsMoleculesOrganellesCells
3 Course OutlineHormone: Definition ,classification dan Fungsi
4 Endocrine System Endocrine glands are ductless Exocrine glands have ducts
5 What is a Hormone A specific chemical compound Produced by a specific tissue of the bodyWhere it is released in the body fluidsAnd carried to a distant target tissueWhere it affects a pre-existing mechanismAnd is effective is small amounts.
6 DefinitionThey are the chemical integrators of a multicellular existence, coordinating activities from daily maintenance to reproduction and development.
7 Hormone Substance produced by endocrine gland Acts on cells, tissues or organs at a place other than where producedActs as a catalyst.
8 Produced by a specific tissue Major Endocrine Organs areHypothalamusPituitary glandThyroid glandParathyroid glandThymusAdrenal glandPancreasOvariesTestes
9 Classification Hormones can be classified by several properties 1. Classification by site of action.1.1. Autocrine secretion - substance released by cell that affects the secreting cell itself(e.g. norepinephrine is released by a neurosecretory cell in the adrenal medulla, andnorepinephrine itself inhibits further release by that cell - this is also an example of direct negative feedback)
10 Endocrine Glands Endocrine glands Paracrine secretions release hormoneshormones travel through blood to target cellsParacrine secretionsact locallyaffect only neighboring cellsAutocrine secretionsaffect only the secreting cell
12 Classification and Properties of Hormone A. Site of ProductionB. Type of action1. Primary hormone of reproduction2. Metabolic hormoneC. Chemical Structure1. General structureProteins and polypeptidesSteroidsFatty acidsModified amino acid2. Size
13 Paracrine secretionsubstance released by cell that affects neighboring cells.Not released into bloodstream (e.g. histamine released at site of injury to constrict blood vessel walls and stop bleeding)Endocrine secretion- substance released by cell into bloodstream that affects distant cells.
15 Types of cell-to-cell signaling Classic endocrine hormones travel via bloodstream to target cells; neurohormones are released via synapses and travel via the bloostream; paracrine hormones act on adjacent cells and autocrine hormones are released and act on the cell that secreted them. Also, intracrine hormones act within the cell that produces them.
17 Function of Hypothalamus appetitethirstbody temperaturevasomotor activityemotionuse of body nutrient reservesactivity of intestinesleepsexual behaviorProduction and release of releasing hormones
18 Cells of the Anterior Pituitary HypothalamusPreoptic nuclei cellNerve CellsSuperior hypophyseal arteryCapillary plexusHypophyseal portal vesselsCells of the Anterior PituitaryPosterior pituitaryLHFSHProlactinSTHTSHACTHCapillary plexus
19 Nuclei that produce posterior pituitary hormones HypothalamusNuclei that produce posterior pituitary hormones
20 Pituitary Gland Control Hypothalamic releasing hormones stimulate cells of anterior pituitary to release hormonesNerve impulses from hypothalamus stimulate nerve endings in the posterior pituitary gland to release hormones
21 Anterior Pituitary Hormones A. Structure1. glycoproteins or proteinsB. Hormones1. gonadotropinsFollicle stimulating hormone (FSH)Luteinizing hormone (LH)Prolactin
42 Hormones – chemical structure and synthesis Proteins and polypeptides –the anterior and posterior pituitary gland hormones, the pancreas (insulin, glucagon), the parathyroidal gland (parathyroidal hormone), etc.Steroids – the adrenal cortex (cortisol, aldosterone), the ovaries (estrogen, progesterone), the testes (testosterone), the placenta (estrogen, progesterone)Derivates of amino acid tyrosine – the thyroid gland (thyroxine, triiodothyronine), the adrenal medullae (epinephrine, norepinephrine)
43 Polypeptide and protein hormones Most of the hormones in the body.Protein = 100 of more amonoacidsPeptides = less than 100 aminoacidsSynthesized in the rough endoplasmatic reticulum as preprohormones prohormones transferred to Golgi apparatus secretory vehicles hormones (enzymatic fission) exocytosisWater soluble – easy reaching the target tissue by circulatory system
44 Steroid hormones Usually synthesized from cholesterol Not stored, but possible quick utilization from cholesterol in the bloodLipid soluble – diffuse across the cell membrane interstitial fluid blood
45 Steroid hormonesAll steroid hormones are derived from cholesterol and differ only in the ring structure and side chains attached to it.All steroid hormones are lipid soluble
46 Types of steroid hormones Glucocorticoids; cortisol is the major representative in most mammalsMineralocorticoids; aldosterone being most prominentAndrogens such as testosteroneEstrogens, including estradiol and estroneProgestogens (also known a progestins) such as progesterone
47 Steroid hormonesAre not packaged, but synthesized and immediately releasedAre all derived from the same parent compound: CholesterolEnzymes which produce steroid hormones from cholesterol are located in mitochondria and smooth ERSteroids are lipid soluble and thus are freely permeable to membranes so are not stored in cells
48 Steroid hormonesSteroid hormones are not water soluble so have to be carried in the blood complexed to specific binding globulins.Corticosteroid binding globulin carries cortisolSex steroid binding globulin carries testosterone and estradiolIn some cases a steroid is secreted by one cell and is converted to the active steroid by the target cell: an example is androgen which secreted by the gonad and converted into estrogen in the brain
49 Steroids can be transformed to active steroid in target cell
52 Steroid hormone synthesis All steroid hormones are derived from cholesterol. A series of enzymatic steps in the mitochondria and ER of steroidogenic tissues convert cholesterol into all of the other steroid hormones and intermediates.The rate-limiting step in this process is the transport of free cholesterol from the cytoplasm into mitochondria. This step is carried out by the Steroidogenic Acute Regulatory Protein (StAR)
53 Steroid hormone synthesis The cholesterol precursor comes from cholesterol synthesized within the cell from acetate, from cholesterol ester stores in intracellular lipid droplets or from uptake of cholesterol-containing low density lipoproteins.Lipoproteins taken up from plasma are most important when steroidogenic cells are chronically stimulated.
60 Amino hormones Derivatives from tyrosine The thyroid hormones Synthesized and stored in follicules in the thyroid gland as thyreoglobulin free hormone to the blood connection to plasma proteins (thyroxine-binding globulin)Adrenal medullary hormonesStored in vesicles exocytosis in the blood as a free hormone or in combination with different substances
61 Amine HormonesTwo other amino acids are used for synthesis of hormones:Tryptophan is the precursor to serotonin and the pineal hormone melatoninGlutamic acid is converted to histamine
62 Fatty Acid Derivatives - Eicosanoids Arachadonic acid is the most abundant precursor for these hormones. Stores of arachadonic acid are present in membrane lipids and released through the action of various lipases. The specific eicosanoids synthesized by a cell are dictated by the battery of processing enzymes expressed in that cell.These hormones are rapidly inactivated by being metabolized, and are typically active for only a few seconds.
63 Fatty Acid Derivatives - Eicosanoids Eicosanoids are a large group of molecules derived from polyunsaturated fatty acids.The principal groups of hormones of this class are prostaglandins, prostacyclins, leukotrienes and thromboxanes.
64 Regulation of hormone secretion Sensing and signaling: a biological need is sensed, the endocrine system sends out a signal to a target cell whose action addresses the biological need. Key features of this stimulus response system are:· receipt of stimulus· synthesis and secretion of hormone· delivery of hormone to target cell· evoking target cell response· degradation of hormone
65 Prostaglandins act locally very potent in small amounts paracrine substancesact locallyvery potent in small amountsregulate cellular responses to hormonescan activate or inhibit adenylate cyclasecontrols cAMP productionalters cell’s response to hormoneswide variety of functions
66 Hormone secretion and blood concentration Norepinephrine, epinephrine -secreted within seconds after the gland is stimulated and develop full action within another few seconds to minutesThyroxine or growth hormone – require months to full effectRates of secretion: μg – mg / dayConcentration in the blood: pg - μg / ml of blood
67 Feedback control of hormone secretion - Negative feedback Prevents overactivity of hormone systemThe control variable is often not the secretory rate of the hormone itself but the degree of activity of the target tissueFeedback regulation of hormones can occur at all levels, including gene transcription and translation steps involved in processing the hormone or releasing the stored hormoneHPA axis (hypothalamo-pituitary-adrenal axis) = complex negative feedback
68 Control of Hormonal Secretions primarily controlled by negative feedback mechanism
70 Complex negative feedback Controlling centers of the CNSNeural pathwaysHypothalamusHypothalamic hormonesAdenohypophysisAdenohypophysal hormonesPeripheral glandsHormones of peripheral glandsTissue
71 Feedback control of hormone secretion - Positive feedback Just in a few instancesPositive feedback occurs when the biological action of the hormone causes additional secretion of the hormoneSecretion of LH (luteinizing hormone) based of the stimulatory effect of estrogen before ovulation – LH stimulates ovaries to produce more estrogen and it stimulates again the pituitary gland to produce LH. When the LH reaches the appropriate concentration the negative feedback occurs
72 Hormone releaseCyclical variation influenced by seasonal changes, stages of development and aging, circadial cycle, sleep etc.STH (growth hormone) – development, ↑ during early period of sleep, ↓ during later stages of sleepGonadal hormones - development and aging, seasonal changes, lunar cyclesACTH, glucocorticoids etc. – circadial cycleReflex release influenced by stress and new situationsStress hormones – corticoids, renin-angiotensin-aldosterone system, prolactin
73 Transport of hormones in the blood Water-soluble hormones (peptides and catecholamines) – dissolved in the plasma, diffusion from capillaries to the interstitial fluid and to target cellsLipid soluble (steroid hormones) and thyroid hormones – circulate in the blood mainly bound to plasma proteins (less then 10% as free hormones).Thyroxine – more than 99% bound to plasma proteins.Hormones bound to proteins are biologically inactive (reservoir) until they dissociate from plasma proteins
74 “Clearance” of hormones from the blood Clearance = rate of disappearance from plasma / concentration in plasma (measuring by radioactive hormone)Ways to clear hormones from plasma:Metabolic destruction by the tissue (enzymes)Binding with the tissue (some hormones may be recycled)Excretion by the liver into the bile (steroid hormones), long-time life period because they are bound to plasma proteins – half-life of thyroid hormones = 1-6 daysExcretion by the kidneys into the urine (peptide hormones and catecholamines = water soluble – short-time life period)
75 Hormone receptors Location: Hormonal receptors are large proteins In or on the surface of the cell membrane – proteins, peptides, catecholaminesIn the cell cytoplasm – steroid hormonesIn the cell nucleus – Thyroid hormonesHormonal receptors are large proteinsEach cell has – receptorsReceptors are usually highly specific for single hormoneThe number of receptors does not remain constant (from day to day, even from minute to minute). Receptors are inactivated or destroyed (down-regulation) and reactivated or produced new ones (up-regulation).
76 Intracellular signaling after hormone receptor activation Different ways of hormone action:Change of membrane permeability (ionotropic receptors), opening and closing ion channels (Na+, K+, Ca2+)of postsynaptic receptors – acetylcholine, norepinephrineActivation of intracellular enzymeKinase promotes phosphorylation – insulinAdenyl cyclase catalyzes the formation of cAMP (cyclic adenosine monophosphate) or cGMP (cyclic guanosin monophosphate) = second messengersBinding with intracellular receptors – steroid and thyroid hormones – hormone-receptor complex activates specific portion of DNA and this initiates transcription of specific genes to form mRNA – protein synthesis (long-term process)
77 The adenylyl cyclase – cAMP second messenger system Hormones:ACTH (Adrenocorticotropic hormone)Angiotensin II (epithelial cells)CalcitoninCatecholamines (β receptors)CRH (Corticotropin-releasing hormone)FSH (Follicle-stimulating hormone)GlucagonHCG (Human chorionic gonadotropin)LH (Luteinizing hormone)PTH (Parathyroid hormone)SecretinTSH (Thyroid-stimulating hormone)Vasopressin (V2 receptor, epithelial cells)
78 The cell membrane phospholipids second messenger system Hormones:Angiotensin II (vascular smooth muscles)Catecholamines (α receptor)GRH (gonadotropin-releasing hormone)GHRH (Growth hormone-releasing hormone)OxytocinTRH (Thyroid-releasing hormone)Vasopressin (V1 receptor, vascular smooth muscle)
79 Hormones acting on the genetic machinery of the cell (1) Steroids:Steroid hormone enters the cytoplasm of the cell and binds to receptor protein (HSP = heat-shock-protein)Receptor protein-hormone complex diffuses or is transported into the nucleusThe complex binds to the DNA and activates the transcription process of specific genes to form mRNAmRNA diffuses into the cytoplasm, promotes translation process at the ribosomes and forms new proteinsExample: Aldosterone (mineralocorticoid from adrenal cortex) acting in renal tubular system. The final effect delays hours after aldosterone enters the cell.
80 Hormones acting on the genetic machinery of the cell (2) Thyroid hormones:Hormones bind directly with receptor proteins in the nucleusThose proteins are probably protein molecules located within the chromosomal complexFunction of thyroid hormones:They activate the genetic mechanisms for the formation of many types of intracellular proteins (100 or more) – many of them are enzymes that control intracellular metabolic activityTheir function of this control may last for days or even weeks
81 Measurement of hormone concentration in the blood RadioimmunoassayHormone specific antibody is mixed with:Animal fluid (serum) containing the hormoneStandard hormone marked by radioactivityHormones (animal’s and standard) compete for this antibodyResult:More radioactive hormone-antibody complex (after separation) = little animal’s hormonesLess radioactive hormone-antibody complex (after separation) = lot of animal’s hormones
84 Hormone ReceptorsA hormone receptor is a receptor protein on the surface of a cell or in its interior that binds to a specific hormone. The hormone causes many changes to take place in the cell. Binding of hormones to hormone receptors often trigger the start of a biophysical signal that can lead to further signal transduction pathways, or trigger the activation or inhibition of genes
85 Types of Hormone Receptors Peptide hormone receptors are often transmembrane proteins. They are also called G-protein-coupled receptors, sensory receptors or ionotropic receptors. These receptors generally function via intracellular second messengers (cAMP)
86 Steroid hormone receptors and related receptors are generally soluble proteins that function through gene activation. These are plasma membrane, cytosol and nucleus. They are generally intracellular receptors.
87 Types of receptors: Type I Receptors : Sex hormone receptors (sex hormones) ; Glucocorticoid receptor (glucocorticoids) ; Mineralocorticoid receptor (mineralocorticoids) Type II Receptors: Thyroid hormone receptor