DOCSLIB.ORG

WRC General Report

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WRC General Report EUROPEAN COMMISSION STUDY ON THE SCIENTIFIC EVALUATION OF 12 SUBSTANCES IN THE CONTEXT OF ENDOCRINE DISRUPTER PRIORITY LIST OF ACTIONS WRc-NSF Ref: UC 6052 NOVEMBER 2002 . STUDY ON THE SCIENTIFIC EVALUATION OF 12 SUBSTANCES IN THE CONTEXT OF ENDOCRINE DISRUPTER PRIORITY LIST OF ACTIONS Report No.: UC 6052 November 2002 Authors: I Johnson and P Harvey Contract Manager: I Johnson Contract No.: 12834-0 RESTRICTION: This report has the following limited distribution: External: Client Internal: Authors and Contract Manager Any enquiries relating to this report should be referred to the authors at the following address: WRc-NSF, Henley Road, Medmenham, Marlow, Buckinghamshire, SL7 2HD. Telephone: + 44 (0)1491 636500 Fax: + 44 (0)1491 636501 The contents of this document are subject to copyright and all rights are reserved. No part of this document may be reproduced, stored in a retrieval system or transmitted, in any form or by any means electronic, mechanical, photocopying, recording or otherwise, without the prior written consent of the copyright owner. This document has been produced by WRc-NSF. European Commission EXECUTIVE SUMMARY 1. Background In June 2001, the Commission adopted a follow up Communication to the Council and European Parliament on the implementation of the Community Strategy for Endocrine Disrupters [COM(2001)262]. In this Communication (EC 2001) the Commission proposed a priority list of actions to further evaluate the role of specific “candidate” substances in endocrine disruption. One of these priority actions was the initiation of an in-depth evaluation of a group of 12 candidate substances consisting of 9 industrial substances (2,2’-bis(4-(2,3- epoxypropyl)phenyl)propane, Carbon disulphide, 4-Chloro-3-methylphenol, 2,4- Dichlorophenol, 4-Nitrotoluene, o-Phenylphenol, Resorcinol, 4-tert Octylphenol and 2,2’,4,4’- Tetrabrominated diphenyl ether or tetra BDE) and three natural/synthetic hormones (Oestrone, Oestradiol and Ethinyloestradiol). This report comprises a review of the 12 substances with the following objectives: 1. Conduct an in-depth evaluation of nine (9) candidate substances for which scientific evidence of endocrine disruption or potential endocrine disruption was identified in the BKH report and which are neither restricted nor currently being addressed under existing Community legislation; 2. Conduct an in-depth evaluation of three (3) synthetic/natural hormones, oestrone, oestradiol and ethinyloestradiol, with a particular focus on up to date evidence of environmental exposure and related effects. 3. Identify specific cases of consumer or ecosystem exposure to these substances, with particular attention to potentially vulnerable consumer groups such as children. At a stakeholder meeting on 21-22 Februray 2002 which discussed the strategy to be adopted for the review a representative from Sweden stated that one of the industrial substances tetra- brominated diphenylether (tetra BDE) was a component of Penta BDE which was in the process of being banned. Therefore, in the interests of efficiency, resources were not assigned to a review of tetra BDE 2. Approach adopted Within the European Commission Strategy for Endocrine Disrupters this report, and the evaluation framework that has been developed, is designed to represent a stage between the identification of potential substances of concern (in a prioritisation) and any potential action following input of these substances into policy discussions. The evaluation framework has been developed to review the nature and extent of endocrine disrupting effects of identified chemicals (and potentially others in the future) and is based on robust datasets. The derived framework is criteria-based (where possible) so that decisions are made in an objective rather than a subjective manner. However, expert judgement is required at each stage and it is important to record the basis of decisions to aid transparency. It also needs to be recognised that the framework does not involve carrying out a full Risk Assessment of a substance under the Existing Substances Regulation 793/93, but it is appropriate to use established procedures from the Technical Guidance Document (EC 1994) where these are relevant. The WRc-NSF - November 2002 5 European Commission adoption of this approach is designed to maximise consistency in terms of terminology used and the procedures adopted (for example in the areas of data relevance and study validity). The developed evaluation framework considers a number of issues most importantly: 1. Does the available data indicate there is evidence that a chemical causes endocrine disrupting effects in target groups of humans and/or wildlife? 2. Do endocrine disrupting effects of the chemical in target groups of humans and/or wildlife occur at lower concentrations than those causing effects on general systemic toxicological endpoints? 3. Are particular target groups of workers, consumers or wildlife organisms in the environment likely to be exposed to concentrations of chemicals which exceed effects thresholds due to current emission patterns. In the review the International Programme for Chemical Safety (IPCS) definition of an endocrine disrupter has been adopted, namely that it is “an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations”. As a result the review considers other mechanisms of action than oestrogenicity and anti-oestrogenicity including androgenicity and anti-androgenicity, effects on thyroid function and effects on hormone secretion and synthesis and steroidogenesis, where relevant data are available. In the context of the review it is recognised that there are various laboratory-based in vivo and in vitro methods utilising a range of (eco)toxicological endpoints that are claimed by different sources to be relevant to the assessment of endocrine disruption in humans and/or wildlife. However, since this field is still in an early stage of development there is uncertainty regarding the significance of many of the current findings. From the numerous recent reviews of potential test methods (such as the Detailed Review Paper prepared by OECD in 1997) there is a clear consensus in terms of the hierarchy of the relevance of test methods. In this hierarchy longer-term in vivo studies considering effects on reproduction and/or development (and including mechanistic information) are of greater relevance than short-term in vivo screening tests which are of greater relevance than in vitro assays. The greater relevance of chronic in vivo tests or those assessing effects during critical windows of sensitivity is also evidenced by the fact that these are the key (eco)toxicological methods being developed in the OECD Endocrine Disruption Testing and Assessment (EDTA) Programme. This hierarchy approach to data relevance has been adopted in the review along with a weight of evidence consideration of the available data. For consideration of the risk of a substance to target groups of humans and/or wildlife a Margin of Safety (MOS) approach has been adopted. The MOS (for consumer use) is calculated by dividing the lowest No Observable Adverse Effect Level (NOAEL) of a compound by its Systemic Exposure Dose (SED) during normal use. If the MOS exceeds 100, the substance is regarded as safe for use. The value of 100 can be modified to account for perceived sensitive target groups (for example children). This approach is based on that given in the Scientific Committee for Consumer Products and Non-Food Products intended for Consumers (SCCNFP) “Notes of Guidance for Testing of Cosmetic Ingredients for their Safety Evaluation” (SCCNFP/0321/00 Final, 2001). A similar approach is applied to workers and also to wildlife groups using appropriate exposure and effects data. It should be recognised that this approach does not provide a as robust a measure of potential risk as a PEC/PNEC WRc-NSF - November 2002 6 European Commission comparison but that it is designed to highlight situations where further effort may be needed to clarify the nature and extent of exposure to a target group. 3. Outcome of the reviews In considering the data on the potential endocrine disrupting effects of individual natural and synthetic substances on target groups of humans and/or wildlife it needs to be recognised that a vast majority of the available data is from studies conducted using current internationally recognised test guidelines or studies carried out using alternative (possibly non-regulatory) procedures. As such the studies may provide information on potential adverse effects on reproduction and development in the species studied but, because they are not specifically designed to address endocrine disruption, do not usually provide data on changes in endocrine function (for example changes in hormone levels). In the assessment of endocrine disruption in humans and wildlife the question of ‘proof’ of adverse effects and of underlying causative factors is crucial both for scientific inference and for guiding opinion forming and decision making. For the industrial substances and natural/synthetic steroids the datasets for assessing potential endocrine disrupting effects in target groups of humans and/or wildlife vary in terms of both the types of studies for which data is available and their reliability (i.e. the methods used and the quality assurance/quality control procedures adopted). This is illustrated in Table ES1 which summarises
Load more

Recommended publications
  • The Immuno-Neuroendocrine Interface
    Amendment history: Erratum (December 2001) Series Introduction: The immuno-neuroendocrine interface Shlomo Melmed J Clin Invest. 2001;108(11):1563-1566. https://doi.org/10.1172/JCI14604. Perspective The CNS and the various endocrine organs are linked in a dynamic manner through networks of reciprocal interactions that allow for both long-term adaptation and short-term shifts in environmental conditions. These regulatory systems embrace the hypothalamus, the pituitary gland, and any of several target glands, including the adrenal gland and the thyroid. Because the anterior pituitary gland secretes at least six key hormones — adrenocorticotropin (ACTH), growth hormone (GH), prolactin (PRL), thyrotropin (TSH), and the gonadotropins follicle stimulating hormone and luteinizing hormone — such diverse parameters as cell integrity, stress responses, growth, development, reproduction, and energy homeostasis are all directly or indirectly under central control (1). In addition, largely because of the dominant role of the hypothalamo-pituitary-adrenal (HPA) axis, inflammation and immunity are also subject to neuroendocrine effects. The articles in this Perspective series explore some of the developmental, physiological, and molecular interactions occurring at the immuno-neuroendocrine interface. Control of pituitary function Three tiers of control subserve regulation of anterior pituitary trophic hormone secretion (2). First, the hypothalamus synthesizes and secretes releasing and inhibiting hormones, which traverse the hypothalamo-pituitary portal system and bind to specific anterior pituitary G protein−linked transmembrane […] Find the latest version: https://jci.me/14604/pdf PERSPECTIVE SERIES Neuro-immune interface Shlomo Melmed, Series Editor SERIES INTRODUCTION The immuno-neuroendocrine interface Shlomo Melmed Cedars-Sinai Research Institute, University of California Los Angeles, School of Medicine, Los Angeles, California 90048, USA.
    [Show full text]
  • Hormone Research
    RECENT PROGRESS IN HORMONE RESEARCH Edited by ANTHONY R. MEANS VOLUME 58 The Human Genome and Endocrinology “Recent Progress in Hormone Research” is an annual publication of The Endocrine Society that is published under the editorial auspices of Endocrine Reviews. The Endocrine Society 8401 Connecticut Avenue, Suite 900 Chevy Chase, Maryland 20815 Copyright 2003 by The Endocrine Society All Rights Reserved The reproduction or utilization of this work in any form or in any electronic, mechanical, or other means, now known or hereafter invented, including photocopying or recording and in any information storage or retrieval system, is forbidden, except as may be expressly permitted by the 1976 Copyright Act or by permission of the publisher. ISBN 0–879225-48-4 CONTENTS Senior Author Correspondence Information v 1. A Functional Proteomics Approach to Signal Transduction 1 Paul R. Graves and Timothy A.J. Haystead 2. The Use of DNA Microarrays to Assess Clinical Samples: The Transition from Bedside to Bench to Bedside 25 John A. Copland, Peter J. Davies, Gregory L. Shipley, Christopher G. Wood, Bruce A. Luxon, and Randall J. Urban 3. Gene Expression Profiling for Prediction of Clinical Characteristics of Breast Cancer 55 Erich Huang, Mike West, and Joseph R. Nevins 4. Statistical Approach to DNA Chip Analysis 75 N.M. Svrakic, O. Nesic, M.R.K. Dasu, D. Herndon, and J.R. Perez-Polo 5. Identification of a Nuclear Factor Kappa B-dependent Gene Network 95 Bing Tian and Allan R. Brasier 6. Role of Defective Apoptosis in Type 1 Diabetes and Other Autoimmune Diseases 131 Takuma Hayashi and Denise L.
    [Show full text]
  • The Endocrine Physiology 2 Inputs That Control Hormone Secretion • Control by Plasma Concentrations of Mineral Ions Or Organic Molecules
    The Endocrine Physiology 2 Inputs that Control Hormone Secretion • Control by Plasma Concentrations of mineral Ions or Organic molecules. For example, absorption of I- iodine ion increase output of thyroxine hormone by thyroid glands. • Control by Neurons – Nervous system can control hormone secretion in 4 ways. 1) Autonomic NS stimulates adrenal medulla to secrete epinephrine 2) Autonomic NS can stimulate or inhibit secretion of a hormone by an endocrine gland 3) neurohormones secreted by hypothalamus pass through blood to anterior pituitary body and influence the secretion of hormones by it. 4) Axons of some neurons of hypothalamus end in posterior pituitary lobe and release their hormones in it. • Control by Other Hormones – when the secretion of a hormone (thyroid stimulating hormone) causes the secretion of another hormone (triodothyronine), the 1st hormone is called a tropic hormone (thyrotropin). Most of these hormones also cause growth of gland (thyroid) secreting the hormone. For this action a tropic hormone is called a trophic hormone. I gave examples in parentheses. Types of Endocrine disorders • Hyposecretion is too little hormone. Primary hyposecretion can be due to partial damage of gland or enzyme deficiency or lack of nutrient in diet or infection etc. Secondary hyposecretion is caused due to deficiency of the tropic hormone though gland is in good condition. • Hypersecretion is too much hormone. It can also be primary or secondary on similar pattern to hyposecretion. • Hyporesponsiveness is reduced responsiveness of target cells to hormone. Most common type of Diabetes mellitus type 2 is caused due to hyporesponsiveness of target cells (muscle cells and adipose tissue).
    [Show full text]
  • UNIT 14 (OPTION) Alterations in Endocrine Function
    UNIT 14 (OPTION) Alterations in Endocrine Function Lorraine Anderson, Ph.D. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 16 Alterations in Endocrine Function 1 Unit 16 Table of Contents Overview....................................................................................................4 Aim ....................................................................................................... 4 Objectives ................................................................................................ 4 Resources................................................................................................. 5 Web Links................................................................................................ 5 Section 1: Mechanisms of Hormone Regulation ....................................................6 Learning Activity #1 ................................................................................... 6 Regulation of Hormone Action ....................................................................... 6 Learning Activity #2 ................................................................................... 7 Hormone Transport .................................................................................... 7 Cellular Mechanisms of Hormone Release ......................................................... 7 Structure and Function of Endocrine Glands....................................................... 9 Hypothalamic Trophic Hormones ................................................................
    [Show full text]
  • Lec . 2 Dr. Shaimaa Munther
    Lec . 2 Dr. Shaimaa Munther • The anterior pituitary ( adenohypophysis) is derived embryonically from glandular tissue, as an invagination of the pharynx called (rathke's pouch). • It then migrates toward the embryonic nervous tissue destined to form the neurohypophysis. • When these two tissues come into contact, the pituitary gland is formed. • Unlike the neurohypophysis, which releases hormones originally synthesized in the hypothalamus, the adenohypophysis synthesizes its own hormones in specialized groups of cells. • Similar to the neurohypophysis, however, the release of these hormones into the blood is regulated by the hypothalamus • The anterior pituitary secretes: 1. Thyroid-stimulating Hormone (TSH, Thyrotropin), 2. Adrenocorticotropic Hormone (ACTH, or called Adrenocorticotropin,or Corticotropin ) 3. Gonadotropines ( Luteinizing Hormone (LH), & Follicle-Stimulating Hormone (FSH)) 4. Prolactin (Lacto tropes) 5. Growth hormone (Somatotropin) • Of the listed hormones, prolactin acts on the breast. the remaining are tropic hormones ; that is, they stimulate secretion of hormonally active substances by other endocrine glands. • Thyroid-stimulating hormone (TSH or Thyrotropin) 1. Regulates the growth and metabolism of the thyroid gland. 2. Stimulates synthesis and release of the thyroid hormones, T3 and T4. • Adrenocorticotropic hormone (ACTH) 1. Stimulates growth of the adrenal cortex 2. Stimulates steroid hormones production in the adrenal cortex. specifically, it stimulates secretion of cortisol and other corticosteroids. • Growth hormone (GH, Somatotropin) 1. Is one of the few hormones that exerts its effects on organs and tissues throughout the body. 2. It is essential for normal growth and development of the skeleton as well as visceral, or soft, tissues from birth until young adulthood. 3. Growth of the skeleton involves : a.
    [Show full text]
  • Introduction to the Endocrine System
    Introduction to the Endocrine System Hormones 7 Hormones Have Been Known Since Ancient Times What Makes a Chemical a Hormone? Hormones Act by Binding to Receptors Hormone Action Must Be Terminated The Classifi cation of Hormones Most Hormones Are Peptides or Proteins Steroid Hormones Are Derived from Cholesterol Some Hormones Are Derived from Single Amino Acids Control of Hormone Release Hormones Can Be Classifi ed by Their Refl ex Pathways The Endocrine Cell Is the Sensor in the Simplest Endocrine Refl exes Many Endocrine Refl exes Involve the Nervous System Neurohormones Are Secreted into the Blood by Neurons The Pituitary Gland Is Actually Two Fused Glands The Posterior Pituitary Stores and Releases Two Neurohormones The Anterior Pituitary Secretes Six Hormones A Portal System Delivers Hormones from Hypothalamus to Anterior The separation Pituitary of the endocrine Anterior Pituitary Hormones Control Growth, Metabolism, and system into isolated Reproduction subsystems must Feedback Loops Are Diff erent in the Hypothalamic-Pituitary Pathway be recognized as an artifi cial one, Hormone Interactions convenient from In Synergism, the Eff ect of Interacting Hormones Is More Than Additive a pedagogical A Permissive Hormone Allows Another Hormone to Exert Its Full Eff ect point of view but Antagonistic Hormones Have Opposing Eff ects not accurately refl ecting the Endocrine Pathologies interrelated nature Hypersecretion Exaggerates a Hormone’s Eff ects of all these systems. Hyposecretion Diminishes or Eliminates a Hormone’s Eff ects Receptor or Second Messenger Problems Cause Abnormal Tissue — Howard Rasmussen, in Responsiveness Williams’ Textbook of Diagnosis of Endocrine Pathologies Depends on the Complexity of the Endocrinology, 1974 R e fl e x Hormone Evolution Background Basics Focus on .
    [Show full text]
  • The Role of Hormones and Trophic Factors As Components of Preservation Solutions in Protection of Renal Function Before Transplantation: a Review of the Literature
    molecules Review The Role of Hormones and Trophic Factors as Components of Preservation Solutions in Protection of Renal Function before Transplantation: A Review of the Literature Aneta Ostró˙zka-Cie´slik 1,* and Barbara Doli ´nska 1,2 1 Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Kasztanowa 3, 41-200 Sosnowiec, Poland; [email protected] 2 “Biochefa” Pharmaceutical Research and Production Plant, Kasztanowa 3, 41-200 Sosnowiec, Poland * Correspondence: [email protected] Academic Editor: Seyed Khosrow Tayebati Received: 16 March 2020; Accepted: 5 May 2020; Published: 7 May 2020 Abstract: Transplantation is currently a routine method for treating end-stage organ failure. In recent years, there has been some progress in the development of an optimal composition of organ preservation solutions, improving the vital functions of the organ and allowing to extend its storage period until implantation into the recipient. Optimizations are mostly based on commercial solutions, routinely used to store grafts intended for transplantation. The paper reviews hormones with a potential nephroprotective effect, which were used to modify the composition of renal perfusion and preservation solutions. Their effectiveness as ingredients of preservation solutions was analysed based on a literature review. Hormones and trophic factors are innovative preservation solution supplements. They have a pleiotropic effect and affect normal renal function. The expression of receptors for melatonin, prolactin, thyrotropin, corticotropin, prostaglandin E1 and trophic factors was confirmed in the kidneys, which suggests that they are a promising therapeutic target for renal IR (ischemia-reperfusion) injury. They can have anti-inflammatory, antioxidant and anti-apoptotic effects, limiting IR injury.
    [Show full text]
  • Endocrine Glands
    ENDOCRINE GLANDS The different activities of the body are regulated by 2 main systems:- 1. The nervous system. 2. The endocrine system. The nervous system: is concerned with regulation of metabolic activities and secretions of glands. It is a rapid control system. The endocrine system: is concerned with regulation of metabolic functions. It is a slow control system. What is meant by the endocrine system? It is a system of ductless glands, which differs from other types of glands such as the salivary glands in that their secretions which are called hormones enter the blood stream directly which carries them to different tissues to produce their effects. What is a hormone ? It is a chemical substance secreted into the blood stream by endocrine glands to act on distant organs called effector organs. Properties of hormones: They are secreted in very small amounts. So, their blood and tissue concentrations are very low. They do not act on the organs secreting them (endocrine glands) but act on distant organs (effector organs). Hormones may act on a specific effector organ e.g. thyrotrophic hormone (TSH) of the anterior pituitary acts specifically on the thyroid gland, or hormones may act on the body as a whole e. g. growth hormone (GH) of the anterior pituitary. Hormones act on the target organ by changing the rate of biochemical reactions in that organ. This effect persists for a longer period even after the hormone which produced it becomes inactivated. Difference between a hormone and an enzyme: Hormone Enzyme Some hormones are All enzymes are proteins. proteins, some are amino acids and some are steroids.
    [Show full text]
  • Mechanisms for Pituitary Tumorigenesis: the Plastic Pituitary
    Mechanisms for pituitary tumorigenesis: the plastic pituitary Shlomo Melmed J Clin Invest. 2003;112(11):1603-1618. https://doi.org/10.1172/JCI20401. Science in Medicine The anterior pituitary gland integrates the repertoire of hormonal signals controlling thyroid, adrenal, reproductive, and growth functions. The gland responds to complex central and peripheral signals by trophic hormone secretion and by undergoing reversible plastic changes in cell growth leading to hyperplasia, involution, or benign adenomas arising from functional pituitary cells. Discussed herein are the mechanisms underlying hereditary pituitary hypoplasia, reversible pituitary hyperplasia, excess hormone production, and tumor initiation and promotion associated with normal and abnormal pituitary differentiation in health and disease. Find the latest version: https://jci.me/20401/pdf SCIENCE IN MEDICINE Mechanisms for pituitary tumorigenesis: the plastic pituitary Shlomo Melmed Cedars-Sinai Medical Center, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA The anterior pituitary gland integrates the repertoire of hormonal signals controlling thyroid, adrenal, reproductive, and growth functions. The gland responds to complex central and peripheral signals by trophic hormone secretion and by undergoing reversible plastic changes in cell growth leading to hyper- plasia, involution, or benign adenomas arising from functional pituitary cells. Discussed herein are the mechanisms underlying hereditary pituitary hypoplasia, reversible pituitary hyperplasia, excess hormone production, and tumor initiation and promotion associated with normal and abnormal pituitary dif- ferentiation in health and disease. J. Clin. Invest. 112:1603–1618 (2003). doi:10.1172/JCI200320401. Introduction tions in genes determining specific pituitary lineages The pituitary gland responds to complex central and (including Prop1, Pit1, and Tpit) are involved in pituitary peripheral signals by two mechanisms.
    [Show full text]
  • An Investigation on Different Mechanisms of Endocrine
    Universitat Autònoma de Barcelona Institut de Ciència i Tecnologia Ambientals AN INVESTIGATION ON DIFFERENT MECHANISMS OF ENDOCRINE DISRUPTION IN FISH AND MOLLUSCS Ph.D. Thesis Angeliki Lyssimachou December 2008 Universitat Autònoma de Barcelona Consell Superior de Investigacions Científiques Institut de Ciència i Tecnologia Instituto de Investigaciones Químicas y Ambientals Ambientales Departamento de Química Ambiental Thesis submitted by Angeliki Lyssimachou in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy (Ph.D.) at the Universitat Autònoma de Barcelona Director: Tutor: Dra. Cinta Porte Visa Dr. Ricardo Marcos Dauder Professor of Investigation Professor Ecotoxicology Group Mutagenesis Group Department of Environmental Departament of Genetics and Chemistry Microbiology IIQAB-CSIC Faculty of Biosciences-UAB “We have to realise that the various forms of life do not construct a pyramid on top of which exists the human species. All the forms of life, construct perhaps a circle, each ring of which is connected with every other. We have to comprehend that the environment does not exist “out there” but “in here”. When we poison the air, the water or the soil, we poison our own selves. Like all the other organisms, we too, form part of a big biological circle, from which nothing can detach us .” John Sind, New South Wales, Australia quoted from “Environment and consciousness in ancient Greece” by Aimilios Bourantinos “What doesn’t kill you, doesn’t necessarily make you stronger ” ACKNOWLEDGMENTS First of all I want to thank my supervisor Dra. Cinta Porte Visa, that without her the realisation of this Ph. D. thesis wouldn’t have been possible.
    [Show full text]
  • In Vitro Studies in Normal and Pygmy T-Lymphoblast Cell Lines
    0031-3998/95/3704-0507$03.00/0 PEDIATRIC RESEARCH Vol. 37. No.4. 1995 Copyright © 1995 International Pediatric Research Foundation, Inc. Printed in US'.A. Growth-Promoting Actions of Parathyroid Hormone, Adrenocorticotrophic Hormone, and Thyroid-Stimulating Hormone: In Vitro Studies in Normal and Pygmy T-Lymphoblast Cell Lines MITCHELL E. GEFFNER, NOELLE BERSCH, ALAN B. CORTEZ, ROBERT C. BAILEY. AND DAVID W. GOLDE Departments of Pediatrics [ M.E. G., N.B., A.B. C.] and Anthropology [ R. C. B.), University of Calijim1ia at Los Angeles, Los Angeles, California 90024, and Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [D. W.G.] BSTR We used an in vitro T-lymphoblast clonal proliferation assay curves). After stimulation with hiGF-1, hPTH, hACTH, and to quantify human IGF-I (hiGF-1)-, human PTH (hPTH)-, human hTSH, the mean peak clonal responses of a pygmy T­ ACTH (hACTH)-, and human TSH (hTSH)-stimulated growth of lymphoblast cell line were 112 :±:: 8.2, 122 :±:: 1.5, 99 :±:: 4.2, and human T-cellleukemia virus-II-transformed T-lymphoblast cell 98 :±:: 5.5%, respectively (all p :S 0.0004 between corresponding lines from normal individuals and to elucidate the role of IGF-I complete pygmy and normal response curves). These data incli­ as the mediator of hPTH-, hACTH-, and hTSH-induced T-cell cate that hPTH, hACTH, and hTSH stimulate growth of normal growth. Normal T-lymphoblast cell lines respond to h!GF-I in a human T-lymphoblast cell lines through local action of IGF-1, bimodal fashion. The mean first peak response was 143 :±:: 9.8% because these effects can all be blocked by preincubation with above baseline (defined as 100%) occurring at 8 j.Lg/L, and the MAb against the IGF-I receptor.
    [Show full text]
  • HUMAN PHYSIOLOGY I (IPHY 3470) 1 Course Learning Goals an Overall
    HUMAN PHYSIOLOGY I (IPHY 3470) LEARNING GOALS (FALL 2012) Course Learning Goals An overall goal of this course is to enable students to understand the role of molecules, cells, tissues, organs, and organ systems (endocrine, nervous, muscular and immune systems) in human health and disease. This class focuses on understanding physiology –the functioning of a living organism and its component parts. This requires going beyond memorization of facts to acquire an understanding of how and why the body functions the way it does, and what happens when it does not function properly. More explicitly, students will able to: 1. Demonstrate an understanding of the physiology and basic regulatory concepts related to the functioning of life processes. The life processes to be studied in IPHY 3470 will include Cell Physiology, Neurophysiology, Endocrinology, Muscle Physiology, and Immunology. 2. Name the key physiology themes (homeostasis & regulation, structure/function relationships, compartmentation, biological energy transformation, and communication & information flow), and be able to provide or recognize examples of each from the different organ systems. 3. Discuss the significance of maintaining homeostasis to the survival of the whole organism. 4. Demonstrate the use of the scientific method and quantitative reasoning to field of physiology. 5. Demonstrate a mechanistic (how) and teleologic (why) understanding of the levels of organization comprising the human organism. 6. Demonstrate an understanding of the physiology and basic regulatory concepts of the organ systems associated with this course and the mechanisms that allow the body to carry out those functions, and predict how a perturbation (e.g., disease, experimental manipulation) will alter function.
    [Show full text]