Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 11 Endocrine Glands Secretion & Action of Hormones 11-1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 11 Outline Overview Chemical Classification of Hormones Hormonal Actions & Interactions Mechanisms of Hormone Action Pituitary Gland Adrenal Gland Thyroid Gland Islets of Langerhans Miscellaneous Glands & Hormone Autocrine & Paracrine Regulation 11-2 Overview 11-3 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endocrine Glands Are ductless & secrete hormones into bloodstream Hormones go to target cells that contain receptor proteins for it Neurohormones are secreted into blood by specialized neurons Hormones affect metabolism of targets Fig 11.1 11-4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 11-5 Chemical Classification of Hormones 11-6 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chemical Classification of Hormones Amine hormones are derived from tyrosine or tryptophan Include NE, Epi, thyroxine, melatonin Polypeptide/protein hormones are chains of amino acids Include ADH, GH, insulin, oxytocin, glucagon, ACTH, PTH Glycoproteins include LH, FSH, TSH Steroids are lipids derived from cholesterol Include testosterone, estrogen, progesterone & cortisol 11-7 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig 11.2 11-8 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chemical Classification of Hormones continued Steroid & thyroid hormones are lipids Can diffuse into target cells The 2 major thyroid hormones are shown in Fig 11.3 11-9 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Prohormones & Prehormones Prohormones are precursors of hormones E.g. proinsulin Prehormones are precursors of prohormones E.g. preproinsulin Some hormones are inactive until activated by target cells E.g. thyroxine (T4) is inactive until converted to T3 in target cells 11-10 Hormonal Actions & Interactions 11-11 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Common Aspects of Neural & Endocrine Regulation Both NS & endocrine system use chemicals to communicate Difference between NTs & hormones is transport in blood & more diversity of effects in hormone targets Some chemicals are used as hormones & NTs Targets for both NTs & hormones must have specific receptor proteins Must be way to rapidly inactivate both 11-12 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hormone Interactions A tissue usually responds to # of hormones 2 hormones are synergistic if work together to produce an effect Produce a larger effect together than individual effects added together A hormone has permissive effect if it enhances responsiveness of a target organ to 2nd hormone If action of 1 hormone inhibits effect of another, it is antagonistic 11-13 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hormone Levels & Tissue Responses Half-life is time required for blood level to be reduced by half Ranges from mins to hrs for most (days for thyroid hormones) Normal tissue responses are produced only when hormones are in physiological range High (pharmacological) doses can cause # of side effects Probably by binding to receptors of other hormones 11-14 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hormone Levels & Tissue Responses continued Priming effect (upregulation) occurs when a hormone induces more of its own receptors in target cells Results in greater response in target cell Desensitization (downregulation) occurs after long exposure to high levels of polypeptide hormone Subsequent exposure to this hormone produces a lesser response Due to decrease in # of receptors on targets Most peptide hormones have pulsatile secretion which prevents downregulation 11-15 Mechanisms of Hormone Action 11-16 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mechanisms of Hormone Action Target cell receptors show specificity, high affinity, & low capacity for a hormone Lipid hormones have receptors in target's cytoplasm &/or nucleus because can diffuse thru plasma membrane Receptors for water-solubles are on surface of target cell 11-17 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hormones That Bind to Nuclear Receptor Proteins Lipid hormones travel in blood attached to carrier proteins They dissociate from carriers to pass thru plasma membrane of target Receptors are called nuclear hormone receptors Fig 11.4 11-18 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nuclear Hormone Receptors Serve as transcription factors when bound to hormone ligands Activate transcription Constitute a "superfamily" composed of steroid family & thyroid hormone family (which includes vitamin D & retinoic acid) 11-19 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nuclear Hormone Receptors Have ligand (hormone)-binding & DNA-binding domains Binds hormone & translocates to nucleus Binds to hormone-response element (HRE) on DNA located adjacent to target gene Fig 11.5 11-20 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mechanisms of Steroid Hormones HRE consists of 2 half- sites 2 ligand-bound receptors have to bind to each HRE (dimerization) This stimulates transcription of target gene Fig 11.5 11-21 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mechanism of Thyroid Hormone Action Thyroid secretes 90% T4 (thyroxine) & 10% T3 99.96% of T4 in blood is bound to carrier protein (thyroid binding globulin - TBG) Only free can enter cells, so bound is reservoir T4 converted to T3 inside cell T3 binds to receptor protein located in nucleus 11-22 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mechanism of Thyroid Hormone Action continued T3 & receptor bind to 1 half-site Other half-site binds retinoic acid Two partners form heterodimer that activates HRE Stimulates transcription of target gene Fig 11.7 11-23 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hormones That Use 2nd Messengers Water soluble hormones use cell surface receptors because cannot pass through plasma membrane Actions are mediated by 2nd messengers Hormone is extracellular signal; 2nd messenger carries signal from receptor to inside of cell 11-24 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Adenylate Cyclase-cAMP Mediates effects of many polypeptide & glycoprotein hormones Hormone binds to receptor causing dissociation of a G-protein subunit Fig 11.8 11-25 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Adenylate Cyclase-cAMP continued G-protein subunit binds to & activates adenylate cyclase Which converts ATP into cAMP cAMP attaches to inhibitory subunit of protein kinase Fig 11.8 11-26 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Adenylate Cyclase-cAMP continued Inhibitory subunit dissociates, activating protein kinase Which phosphorylates enzymes that produce hormone’s effects cAMP inactivated by phosphodiesterase Fig 11.8 11-27 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Phospholipase-C-Ca2+ Serves as 2nd messenger system for some hormones Hormone binds to surface receptor, activates G-protein, which activates phospholipase C Fig 11.9 11-28 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Phospholipase-C-Ca2+ Phospholipase C splits a membrane phospholipid into 2nd messengers IP3 & DAG IP3 diffuses through cytoplasm to ER Causing Ca2+ channels to open Fig 11.9 11-29 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Phospholipase-C-Ca2+ continued Ca2+ diffuses into cytoplasm & binds to & activates calmodulin Ca2+-Calmodulin activates protein kinases which phosphorylate enzymes that produce hormone's effects 11-30 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Epi Can Act Via Two 2nd Messengers Fig 11.10 11-31 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Tyrosine Kinase 2nd Messenger System Is used by insulin & many growth factors to cause cellular effects Surface receptor is tyrosine kinase Consists of 2 units that form active dimer when insulin binds Fig 11.11 11-32 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Tyrosine Kinase 2nd Messenger System Activated tyrosine kinase phosphorylates signaling molecules that induce hormone/growth factor effects Fig 11.11 11-33 Pituitary Gland 11-34 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pituitary Gland Pituitary gland is located beneath hypothalamus at base of forebrain Fig 8.16 11-35 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pituitary Gland continued Is structurally & functionally divided into anterior & posterior lobes Hangs below hypothalamus by infundibulum Anterior produces own hormones Controlled by hypothalamus Posterior stores & releases hormones made in hypothalamus Fig 11.12 11-36 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Anterior Pituitary Secretes 6 trophic hormones that maintain size of targets High blood levels cause target to hypertrophy Low levels cause atrophy 11-37 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Anterior Pituitary continued Growth hormone (GH) promotes growth, protein synthesis, & movement of amino acids into cells Thyroid stimulating hormone (TSH) stimulates thyroid to produce & secrete T4 & T3 Adrenocorticotrophic hormone (ACTH) stimulates adrenal cortex to secrete cortisol, aldosterone Follicle stimulating hormone (FSH) stimulates growth of ovarian follicles & sperm production Luteinizing hormone (LH) causes ovulation & secretion of testosterone in testes Prolactin (PRL) stimulates milk production by mammary glands 11-38 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Anterior Pituitary continued Release of A. Pit. hormones is controlled by hypothalamic releasing & inhibiting factors & by feedback from levels of target gland hormones 11-39 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Anterior Pituitary continued Releasing & inhibiting hormones from hypothalamus are released from axon endings into capillary bed in median eminence Carried by hypothalamohypophyseal portal system directly to another capillary bed in A. Pit. Diffuse into A. Pit. & regulate secretion of its hormones Fig 11.15 11-40 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Feedback Control of Anterior Pituitary Involves short feedback loop in which retrograde flow of blood & hormones from A. Pit. to hypothalamus inhibits secretion of releasing hormone Involves negative feedback of target gland hormones & during menstrual cycle, estrogen stimulates “LH surge” by positive feedback Fig 11.17 11-41 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Higher Brain Function & Anterior Pituitary Secretion Hypothalamus receives input from higher brain centers that can affect A. Pit. secretion E.g. psychological stress affects circadian rhythms, menstrual cycle, & adrenal hormones 11-42 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Posterior Pituitary Stores & releases 2 hormones produced in hypothalamus: Antidiuretic hormone (ADH/vasopressin) which promotes H20 conservation by kidneys Oxytocin which stimulates contractions of uterus during parturition & contractions of mammary gland alveoli for milkejection reflex 11-43 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hypothalamic Control of Posterior Pituitary Supraoptic nuclei of hypothalamus produce ADH Paraventricular nuclei produce oxytocin Both transported along hypothalamohypophyseal tract to posterior pituitary Release controlled in hypothalamus by neuroendocrine reflexes Fig 11.13 11-44 Adrenal Gland 11-45 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Adrenal Glands Sit on top of kidneys Each consists of outer cortex & inner medulla 2 arise differently during development Fig 11.18 11-46 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Adrenal Glands Medulla synthesizes & secretes 80% Epi & 20% NE Controlled by sympathetic Cortex is controlled by ACTH & secretes: Cortisol which inhibits glucose utilization & stimulates gluconeogenesis Aldosterone which stimulate kidneys to reabsorb Na+ and secrete K+ & some supplementary sex steroids 11-47 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Adrenal Cortex Fig 11.19 11-48 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Adrenal Medulla Hormonal effects of Epi last 10X longer than NE Innervated by preganglionic Symp fibers Activated during "fight or flight" response Causes: Increased respiratory rate Increased HR & cardiac output General vasoconstriction which increases venous return Glycogenolysis & lipolysis 11-49 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Stress & the Adrenal Gland Stress induces a nonspecific response called general adaptation syndrome (GAS) Causes ACTH & cortisol release Often affects physiology negatively Fig 11.20 11-50 Thyroid Gland 11-51 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Thyroid Gland Is located just below the larynx Secretes T4 & T3 which set BMR & are needed for growth, development Fig 11.21 11-52 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Thyroid Gland Consists of microscopic thyroid follicles Outer layer is follicle cells that synthesize T4 Interior filled with colloid, a protein-rich fluid 11-53 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Production of Thyroid Hormones (I-) in blood is actively transported into follicles & secreted into colloid Where it is oxidized to iodine (I2) & attached to tyrosines of thyroglobulin A large storage molecule for T4 & T3 TSH stimulates hydrolysis of T4 & T3s from thyroglobulin & then secretion Iodide Fig 11.23 11-54 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diseases of the Thyroid - Goiter In absence of sufficient dietary iodide, T4 & T3 cannot be made & levels are low Low T4 & T3 don’t provide negative feedback & TSH levels go up Because TSH is a trophic hormone, thyroid gland grows Resulting in a goiter Fig 11.25 11-55 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diseases of the Thyroid - Hypothyroidism People with inadequate T4 & T3 levels are hypothyroid Have low BMR, weight gain, lethargy, cold intolerance & myxedema = puffy face, hands, feet During fetal development hypothyroidism can cause cretenism (severe mental retardation) 11-56 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diseases of the Thyroid - Hyperthyroidism Goiters are also produced by Grave's disease Autoimmune disease where antibodies act like TSH & stimulate thyroid gland to grow & oversecrete = hyperthyroidism Characterized by exopthalmos, weight loss, heat intolerance, irritability, high BMR 11-57 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 11-58 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Parathyroid Glands Are 4 glands embedded in lateral lobes of thyroid gland Secrete Parathyroid hormone (PTH) Most important hormone for control of blood Ca2+ levels Fig 11.28 11-59 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Parathyroid Hormone Release stimulated by decreased blood Ca2+ Acts on bones, kidney, & intestines to increase blood Ca2+ levels Fig 11.29 11-60 Islets of Langerhans 11-61 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Islets of Langerhans Are scattered clusters of endocrine cells in pancreas Contain alpha & beta cells Fig 11.30 11-62 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Islets of Langerhans continued Alphas secrete glucagon in response to low blood glucose Stimulates glycogenolysis & lipolysis Increases blood glucose 11-63 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Islets of Langerhans continued Betas secrete insulin in response to low blood glucose Promotes entry of glucose into cells & conversion of glucose into glycogen & fat Decreases blood glucose Fig 11.31 11-64 Miscellaneous Glands & Hormones 11-65 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pineal Gland Is located in basal forebrain near thalamus Secretes melatonin in response to activity of suprachiasmatic nucleus (SCN) of hypothalamus Fig 11.32 11-66 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pineal Gland continued SCN is primary timing center for circadian rhythms Reset by daily light/dark changes Melatonin is involved in aligning physiology with sleep/wake cycle & seasons Secreted at night & is inhibited by light Inhibits GnRH (antigonadotropic) in many animals 11-67 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Thymus Is located around trachea below thyroid Produces T cells of immune system & hormones that stimulate them Fig 11.33 11-68 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Sex & Reproductive Hormones Gonads (testes & ovaries) secrete steroid hormones testosterone, estrogen, & progesterone Placenta secretes estrogen, progesterone, hCG, and somatomammotropin 11-69 Autocrine & Paracrine Regulation 11-70 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Autocrine & Paracrine Regulation Autocrine regulators are produced & act within same tissue of an organ All autocrines control gene expression in target cells Paracrine regulators are autocrines that are produced within one tissue & act on different tissue in same organ. Autocrines & paracrines include: Cytokines (lymphokines, interleukins) Growth factors (promote growth & cell division) Neutrophins (provides trophic support for normal & regenerating neurons) 11-71 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Prostaglandins (PGs) Are produced in almost every organ Belong to eicosanoid family -- all derived from arachidonic acid of plasma membrane Fig 11.34 11-72 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Prostaglandins (PGs) continued Have wide variety of functions Different PGs may exert antagonistic effects in tissues Some promote smooth muscle contraction & some relaxation Some promote clotting; some inhibit Promotes inflammatory process of immune system Plays role in ovulation Inhibits gastric secretion in digestive system 11-73 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Prostaglandins (PGs) continued Cyclooxygenase (COX) 1 & 2 are involved in PG synthesis (Fig 11.34) Are targets of a number of inhibitory non-steroidal antiinflammatory drugs (NSAIDs) Aspirin, indomethacin, ibuprofen inhibit both COX 1 & 2 thereby producing side effects Celebrex & Vioxx only inhibit COX 2 & thus have few side effects 11-74