Presentation on theme: "Hormone ?? PROGRAM KEDOKTERAH HEWAN UNIVERSITAS BRAWIJAYA."— Presentation transcript:
Hormone ?? PROGRAM KEDOKTERAH HEWAN UNIVERSITAS BRAWIJAYA
Organism levelOrgan system level Organ and Tissue levels Cellular level Macromolecular level Molecular level 0.2 mm20 µm2 µm200 nm20 nm2 nm0.2 nm Atoms Molecules Organelles Cells Biological function at each level of organization
Course Outline Hormone: Definition,classification dan Fungsi
Endocrine System 4 Endocrine glands are ductless Exocrine glands have ducts
A specific chemical compound Produced by a specific tissue of the body Where it is released in the body fluids And carried to a distant target tissue Where it affects a pre-existing mechanism And is effective is small amounts.
Definition They are the chemical integrators of a multicellular existence, coordinating activities from daily maintenance to reproduction and development.
Hormone Substance produced by endocrine gland Acts on cells, tissues or organs at a place other than where produced Acts as a catalyst.
Major Endocrine Organs are Hypothalamus Pituitary gland Thyroid gland Parathyroid gland Thymus Adrenal gland Pancreas Ovaries Testes
Classification Hormones can be classified by several properties 1. Classification by site of action 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, and norepinephrine itself inhibits further release by that cell - this is also an example of direct negative feedback)
Endocrine Glands 10 Endocrine glands release hormones hormones travel through blood to target cells Paracrine secretions act locally affect only neighboring cells Autocrine secretions affect only the secreting cell
Classification and Properties of Hormone A.Site of Production B.Type of action 1.Primary hormone of reproduction 2.Metabolic hormone C.Chemical Structure 1. General structure Proteins and polypeptides Steroids Fatty acids Modified amino acid 2. Size
Paracrine secretion -substance 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.
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.
Function of Hypothalamus appetite thirst body temperature vasomotor activity emotion use of body nutrient reserves activity of intestine sleep sexual behavior Production and release of releasing hormones
Cells of the Anterior Pituitary LH FSH Prolactin STH TSH ACTH Hypothalamus Nerve Cells Superior hypophyseal artery Hypophyseal portal vessels Capillary plexus Posterior pituitary Capillary plexus Preoptic nuclei cell
Hypothalamus Nuclei that produce posterior pituitary hormones
Pituitary Gland Control 20 Hypothalamic releasing hormones stimulate cells of anterior pituitary to release hormones Nerve impulses from hypothalamus stimulate nerve endings in the posterior pituitary gland to release hormones
Gonads: Sex hormones: Oestrogen, progesterone, testosterone.
Classification and Properties of Hormone Chemical Structure Polypeptides - hypothalamic Protein - pituitary, gonad Steroids - gonad, adrenal Fatty acid - many sources, prostaglandins Modified amino acid - pineal
Chemistry of Hormones 35 Steroid or Steroid-Like Hormones sex hormones adrenal cortex hormones Nonsteroid Hormones amines proteins peptides glycoproteins most hormones
Chemical Structure of Hormones polypeptidemodified amino acidproteinsex steroidfatty acid GnRhmelatoninLH EstradiolPGF TRHFSH Progesterone CRHProlactinTestosterone GHRHACTH SomatistatinTSH OxytocinGH or STH Relaxin Inhibin 2
Chemical Structure of Hormones FSH30,000 to 37,000 LH26,000 to 32,000 Prolactin23,000 to 25,000 HCG37,700 eCG28,000 Inhibin>10,000 Relaxin6,500 ACTH4,500 Oxytocin1,007 GnRH1,200 Estradiol300 Testosterone300 Progesterone300 PGF300 Molecular size of hormones that regulate reproduction HormoneMolecular Weight 2
Chemical Structure of Hormones Cont. Polypeptide and protein hormones are made of peptide bonds These hormones can not be given orally!
Chemical Structure of Hormones Cont. Steroids PROGESTERONE CORTISOL These hormones can be given orally!
Types of Hormones 40
Structural Formulas of Hormones 41
Hormones – chemical structure and synthesis 1.Proteins and polypeptides –the anterior and posterior pituitary gland hormones, the pancreas (insulin, glucagon), the parathyroidal gland (parathyroidal hormone), etc. 2.Steroids – the adrenal cortex (cortisol, aldosterone), the ovaries (estrogen, progesterone), the testes (testosterone), the placenta (estrogen, progesterone) 3.Derivates of amino acid tyrosine – the thyroid gland (thyroxine, triiodothyronine), the adrenal medullae (epinephrine, norepinephrine)
Polypeptide and protein hormones Most of the hormones in the body. Protein = 100 of more amonoacids Peptides = less than 100 aminoacids Synthesized in the rough endoplasmatic reticulum as preprohormones prohormones transferred to Golgi apparatus secretory vehicles hormones (enzymatic fission) exocytosis Water soluble – easy reaching the target tissue by circulatory system
Steroid hormones Usually synthesized from cholesterol Not stored, but possible quick utilization from cholesterol in the blood Lipid soluble – diffuse across the cell membrane interstitial fluid blood
Steroid hormones All 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
Types of steroid hormones Glucocorticoids; cortisol is the major representative in most mammals Mineralocorticoids; aldosterone being most prominent Androgens such as testosterone Estrogens, including estradiol and estrone Progestogens (also known a progestins) such as progesterone
Steroid hormones Are not packaged, but synthesized and immediately released Are all derived from the same parent compound: Cholesterol Enzymes which produce steroid hormones from cholesterol are located in mitochondria and smooth ER Steroids are lipid soluble and thus are freely permeable to membranes so are not stored in cells
Steroid hormones Steroid hormones are not water soluble so have to be carried in the blood complexed to specific binding globulins. Corticosteroid binding globulin carries cortisol Sex steroid binding globulin carries testosterone and estradiol In 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
Steroids can be transformed to active steroid in target cell
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)
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.
cholesterol Extracellular lipoprotein Cholesterol pool LH ATP cAMP PKA+ Pregnenolone Progesterone Androstenedione TESTOSTERONE 3 HSD P450c17 17 HSD acetate
Cholesterol is a 17 ketosteroid and an important precursor for all steroid hormones.
Actions of Steroid Hormones 56 hormone crosses membranes hormone combines with receptor in nucleus synthesis of mRNA activated mRNA enters cytoplasm to direct synthesis of protein
Actions of Steroid Hormones 57
Actions of Nonsteroid Hormones 58 adenylate cyclase activated hormone binds to receptor on cell membrane ATP converted to cAMP cAMP promotes a series of reactions leading to cellular changes
Actions of Nonsteroid Hormones 59
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 hormones Stored in vesicles exocytosis in the blood as a free hormone or in combination with different substances
Amine Hormones Two other amino acids are used for synthesis of hormones: Tryptophan is the precursor to serotonin and the pineal hormone melatonin Glutamic acid is converted to histamine
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.
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.
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
Prostaglandins 65 paracrine substances act locally very potent in small amounts regulate cellular responses to hormones can activate or inhibit adenylate cyclase controls cAMP production alters cells response to hormones wide variety of functions
Hormone secretion and blood concentration Norepinephrine, epinephrine -secreted within seconds after the gland is stimulated and develop full action within another few seconds to minutes Thyroxine or growth hormone – require months to full effect Rates of secretion: μg – mg / day Concentration in the blood: pg - μg / ml of blood
Feedback control of hormone secretion - Negative feedback Prevents overactivity of hormone system The control variable is often not the secretory rate of the hormone itself but the degree of activity of the target tissue Feedback regulation of hormones can occur at all levels, including gene transcription and translation steps involved in processing the hormone or releasing the stored hormone HPA axis (hypothalamo-pituitary-adrenal axis) = complex negative feedback
Control of Hormonal Secretions 68 primarily controlled by negative feedback mechanism
Negative Feedback 69
Complex negative feedback Controlling centers of the CNS Neural pathways Hypothalamus Hypothalamic hormones Adenohypophysis Adenohypophysal hormones Peripheral glands Hormones of peripheral glands Tissue
Feedback control of hormone secretion - Positive feedback Just in a few instances Positive feedback occurs when the biological action of the hormone causes additional secretion of the hormone Secretion 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
Hormone release Cyclical 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 sleep Gonadal hormones - development and aging, seasonal changes, lunar cycles ACTH, glucocorticoids etc. – circadial cycle Reflex release influenced by stress and new situations Stress hormones – corticoids, renin-angiotensin- aldosterone system, prolactin
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 cells Lipid 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
Clearance of hormones from the bloodClearance 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 days Excretion by the kidneys into the urine (peptide hormones and catecholamines = water soluble – short-time life period)
Hormone receptors Location: In or on the surface of the cell membrane – proteins, peptides, catecholamines In the cell cytoplasm – steroid hormones In the cell nucleus – Thyroid hormones Hormonal receptors are large proteins Each cell has – receptors Receptors are usually highly specific for single hormone The 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).
Intracellular signaling after hormone receptor activation Different ways of hormone action: Change of membrane permeability (ionotropic receptors), opening and closing ion channels (Na +, K +, Ca 2+ )of postsynaptic receptors – acetylcholine, norepinephrine Activation of intracellular enzyme Kinase promotes phosphorylation – insulin Adenyl cyclase catalyzes the formation of cAMP (cyclic adenosine monophosphate) or cGMP (cyclic guanosin monophosphate) = second messengers Binding 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)
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) Oxytocin TRH (Thyroid-releasing hormone) Vasopressin (V1 receptor, vascular smooth muscle)
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 nucleus The complex binds to the DNA and activates the transcription process of specific genes to form mRNA mRNA diffuses into the cytoplasm, promotes translation process at the ribosomes and forms new proteins Example: Aldosterone (mineralocorticoid from adrenal cortex) acting in renal tubular system. The final effect delays hours after aldosterone enters the cell.
Hormones acting on the genetic machinery of the cell (2) Thyroid hormones: Hormones bind directly with receptor proteins in the nucleus Those proteins are probably protein molecules located within the chromosomal complex Function 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 activity Their function of this control may last for days or even weeks
Measurement of hormone concentration in the blood Radioimmunoassay Hormone specific antibody is mixed with: Animal fluid (serum) containing the hormone Standard hormone marked by radioactivity Hormones (animals and standard) compete for this antibody Result: More radioactive hormone-antibody complex (after separation) = little animals hormones Less radioactive hormone-antibody complex (after separation) = lot of animals hormones
Hormone Receptors A 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.receptor proteinhormone 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 genessignal transduction pathways
Types of Hormone Receptors Peptide hormonePeptide 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)transmembrane proteinsG-protein-coupled receptorssensory receptorsionotropic receptorssecond messengers
Steroid hormone receptorsSteroid 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.plasma membranecytosolnucleusintracellular receptors
Types of receptors: Type I Receptors : Sex hormone receptors (sex hormones) ; Glucocorticoid receptor (glucocorticoids) ; Mineralocorticoid receptor (mineralocorticoids)Sex hormone receptorssex hormones Glucocorticoid receptorglucocorticoids Mineralocorticoid receptormineralocorticoids Type II Receptors: Thyroid hormone receptorThyroid hormone receptor