Endocrine System Lecture Notes PDF

Endocrine System Lecture 51 – Chapter 7 Sai Sudha Koka, PhD., RPh Associate Professor Department of Pharmaceutical Sciences Irma Lerma Rangel School of Pharmacy Texas A&M University Kingsville, TX 78363 Phone: 361-221-0758 e-mail: [email protected]...

Endocrine System Lecture 51 – Chapter 7 Sai Sudha Koka, PhD., RPh Associate Professor Department of Pharmaceutical Sciences Irma Lerma Rangel School of Pharmacy Texas A&M University Kingsville, TX 78363 Phone: 361-221-0758 e-mail: [email protected] Office: Room 304  Chapter 7 Overview of the endocrine system The classification of Hormones Control of Hormone Release Hormone interaction Endocrine Pathologies Hormone Evolution  Learning Objectives  Describe the endocrine system including all the organs of the endocrine system  Explain the criteria that make a chemical signal a hormone and explain the mechanism of action of a hormone.  List the classes of hormones with example of each and identify the function of various endocrine hormones (prolactin, TSH, ACTH. GH, FSH and LH).  Compare and contrast the synthesis, secretion and targets of various endocrine hormones.  Explain endocrine hormone interactions such as permissiveness, synergism, functional antagonism and feedback loops as they apply to hormones.  Hormones Cell-to-cell communication molecules – Chemical signals – Secreted by a cell or group of cells into the blood – Transported by blood – Distant target tissue receptors Growth factors act at short distance – Activates physiological response at low concentrations Ectohormones are released into the environment Pheromones: Elicit physiological or behavioral response on other organisms of the same species  Hormones Function They control – Rates of enzymatic reactions – Transport of ions or molecules across cell membranes – Gene expression and protein synthesis Cellular mechanism of action – Depends on binding to target cell receptors – Initiates biochemical responses Hormone action must be terminated – Half-life indicates length of activity  Hormones: Classification by Chemical Class Peptide or protein hormones Steroid hormones Amino acid–derived or amine hormones List of Hormones in Human Body Comparison of Peptide, Steroid and AA-Derived Hormones  Hormones: Peptides or Proteins Preprohormone – Large, inactive precursor Prohormone – Smaller, inactive Proteolytic, post-translational modification Peptide/protein hormones – Transport in the blood and half-life – Bind surface membrane receptors – Cellular response through signal transduction system Peptide Hormone Synthesis and Processing  Slide 2 Messenger RNA on the mRNA ribosomes binds amino acids into a peptide chain called a Preprohormone Ribosome preprohormone. The chain is directed into Endoplasmic the ER lumen by a reticulum (ER) signal sequence of amino acids. Cytoplasm ECF Plasma Capillary endothelium  Slide 3 Messenger RNA on the mRNA ribosomes binds amino acids into a peptide chain called a Preprohormone Ribosome preprohormone. The chain is directed into Endoplasmic the ER lumen by a reticulum (ER) signal sequence of amino acids. Signal Prohormone sequence Enzymes in the ER chop off the signal sequence, creating an inactive prohormone. Cytoplasm ECF Plasma Capillary endothelium  Slide 4 Messenger RNA on the mRNA ribosomes binds amino acids into a peptide chain called a Preprohormone Ribosome preprohormone. The chain is directed into Endoplasmic the ER lumen by a reticulum (ER) signal sequence of amino acids. Signal Prohormone Transport sequence vesicle Enzymes in the ER chop off the signal sequence, creating an inactive prohormone. The prohormone passes from the ER through the Golgi complex. Golgi complex Cytoplasm ECF Plasma Capillary endothelium  Slide 5 Messenger RNA on the mRNA ribosomes binds amino acids into a peptide chain called a Preprohormone Ribosome preprohormone. The chain is directed into Endoplasmic the ER lumen by a reticulum (ER) signal sequence of amino acids. Signal Prohormone Transport sequence vesicle Enzymes in the ER chop off the signal sequence, creating an inactive prohormone. The prohormone passes from the ER through the Golgi complex. Golgi complex Secretory vesicles containing enzymes and prohormone bud off the Golgi. The enzymes chop the prohormone into one or more active peptides plus additional peptide Secretory fragments. vesicle Active hormone Cytoplasm Peptide fragment ECF Plasma Capillary endothelium  Slide 6 Messenger RNA on the mRNA ribosomes binds amino acids into a peptide chain called a Preprohormone Ribosome preprohormone. The chain is directed into Endoplasmic the ER lumen by a reticulum (ER) signal sequence of amino acids. Signal Prohormone Transport sequence vesicle Enzymes in the ER chop off the signal sequence, creating an inactive prohormone. The prohormone passes from the ER through the Golgi complex. Golgi complex Secretory vesicles containing enzymes and prohormone bud off the Golgi. The enzymes chop the prohormone into one or more active peptides plus additional peptide Secretory fragments. vesicle Active hormone Cytoplasm Peptide fragment Release The secretory vesicle signal releases its contents by exocytosis into the ECF extracellular space. Plasma Capillary endothelium  Slide 7 Messenger RNA on the mRNA ribosomes binds amino acids into a peptide chain called a Preprohormone Ribosome preprohormone. The chain is directed into Endoplasmic the ER lumen by a reticulum (ER) signal sequence of amino acids. Signal Prohormone Transport sequence vesicle Enzymes in the ER chop off the signal sequence, creating an inactive prohormone. The prohormone passes from the ER through the Golgi complex. Golgi complex Secretory vesicles containing enzymes and prohormone bud off the Golgi. The enzymes chop the prohormone into one or more active peptides plus additional peptide Secretory fragments. vesicle Active hormone Cytoplasm Peptide fragment Release The secretory vesicle signal releases its contents by exocytosis into the ECF extracellular space. Plasma The hormone moves Capillary To target into the circulation for endothelium transport to its target. Peptide Hormone Receptors and Signal Transduction  Steroid Hormones Cholesterol-derived – Made only in a few organs: adrenal glands and gonads Lipophilic and easily cross membranes – Made as needed, not stored Bind carrier proteins in blood – Longer half-life Cytoplasmic or nuclear receptors – Genomic effect to activate or repress genes for protein synthesis – Slower acting Cell membrane receptors – Nongenomic responses Steroid Hormones - Synthesis Steroid Hormones – Mechanism of Action Blood Steroid Cell surface receptor 1 Most hydrophobic steroids are bound to vessel hormone plasma protein carriers. Only unbound hormones can diffuse into the target cell. 2a Rapid responses 1 2 Steroid hormone receptors are in the Protein 2 cytoplasm or nucleus. carrier Nucleus 2a Some steroid hormones also bind to Cytoplasmic membrane receptors that use second Nuclear receptor receptor messenger systems to create rapid cellular responses. Interstitial fluid Cell membrane Steroid Hormones – Mechanism of Action Blood Steroid Cell surface receptor 1 Most hydrophobic steroids are bound to vessel hormone plasma protein carriers. Only unbound hormones can diffuse into the target cell. 2a Rapid responses 1 2 Steroid hormone receptors are in the Protein 2 cytoplasm or nucleus. carrier Nucleus 2a Some steroid hormones also bind to Cytoplasmic membrane receptors that use second Nuclear receptor receptor messenger systems to create rapid cellular responses. DNA Interstitial 3 The receptor-hormone complex binds to fluid DNA and activates or represses one or more genes. 3 Cell membrane Steroid Hormones – Mechanism of Action  Hormones: Amino Acid-Derived or Amine Derived from one of two amino acids – Tryptophan; melatonin – Tyrosine: catecholamines (epinephrine, dopamine) and thyroid hormones Amine hormones: Examples – Melatonin – Catecholamines Epinephrine, Norepinephrine Dopamine Thyroid hormones – Triiodothyronine and thyroxine Endocrine Reflex Control Pathways Endocrine Reflex Pathways Hormones  Hormones Location Hormone Primary Target(s) Main Effect(s) Pineal gland Melatonin [A] Brain, other tissues Circadian rhythms; immune function; antioxidant Hypothalamus (N) Trophic hormones [P] (see Fig. 7.8) Anterior pituitary Release or inhibit pituitary hormones Posterior Oxytocin [P] Vasopressin Breast and uterus Milk ejection; labor and delivery; behavior pituitary (N) (ADH) [P] Kidney Water reabsorption Anterior pituitary (G) Prolactin [P] Breast Liver Milk production Growth hormone (somatotropin) [P] Many tissues Growth factor secretion Growth and metabolism Adrenal cortex Cortisol release Corticotropin (ACTH) [P] Thyroid gland Thyroid hormone synthesis Thyrotropin (TSH) [P] Gonads Gonads Egg or sperm production; sex hormone production Sex Follicle-stimulating hormone [P] hormone production; egg or sperm production Luteinizing hormone [P] KEY G gland C endocrine cells N neurons P peptide S steroid A amino acid–derived  Neurohormones: Major Groups Adrenal medulla – Catecholamines (Epinephrine, Norepinephrine) Hypothalamus – (TRH, CRH, GHRH, GnRH, Dopamine(PIH), Somatostatin) Pituitary gland is two glands fused in one Posterior pituitary is neural tissue and secretes two neurohormones: vasopressin (antidiuretic hormone or ADH) and oxytocin. Anterior pituitary is endocrine tissue and six hormones: prolactin, thyrotropin, adrenocorticotropin, growth hormone, follicle-stimulating hormone, and luteinizing hormone.  The Pituitary Gland HYPOTHALAMUS The pituitary gland sits in a protected pocket of bone, connected to the brain by a thin stalk. Infundibulum is the stalk that connects the pituitary to the brain. Sphenoid bone Posterior pituitary is an extension of the neural tissue. Anterior pituitary is a true endocrine gland of ANTERIOR POSTERIOR epithelial origin. Anterior Pituitary Gland Hormones Posterior Pituitary Gland Hormones Posterior Pituitary Gland Hormones  Endocrine Control A trophic hormone controls the secretion of another hormone Hypothalamic-hypophyseal (pituitary) portal system Three integrating centers – Hypothalamic stimulation—from CNS – Anterior pituitary stimulation—from hypothalamic trophic hormones – Endocrine gland stimulation—from anterior pituitary trophic hormones (except prolactin) Cortisol  Endocrine Control Anterior pituitary hormones control growth, metabolism, and reproduction Negative feedback loops – Short-loop pathway Parathyroid – Long-loop pathway Cortisol Hypothalamic-Pituitary Pathway Hypothalamic-Pituitary Pathway The Growth Hormone Pathway Negative Feedback in Complex Endocrine Pathways Negative Feedback in Complex Endocrine Pathways  Hormone Interactions Synergism – Combined effect is greater than the sum of individual effects Permissiveness – Need second hormone to get full effect Antagonism – One substance opposes the action of another – Competitive inhibitors vs. functional antagonism – Glucagon opposes insulin Synergism  Endocrine Pathologies Hypersecretion: excess hormone – Caused by tumors or exogenous iatrogenic treatment – Negative feedback may lead to atrophy of gland Hyposecretion: deficient hormone – Caused by decreased synthesis materials or atrophy – Absence of negative feedback leads to overproduction of trophic hormones  Endocrine Pathologies: Abnormal Receptors Down-regulation – Decreased number of receptors – Hyperinsulinemia Receptor and signal transduction abnormalities – Missing or nonfunctional receptors – Androgen insensitivity syndrome – Pseudohypothyroidism  Hormone Evolution Evolutionary conservation of hormone function Proteomics – Calcitonin gene-related peptide example Vestigial – Melanocyte-stimulating hormone example Comparative endocrinology – Pineal gland and melatonin example – Melatonin plays a role in sleep-wake cycle and internal clock The Pineal Gland Thank You