Regulation of Organ and Tissue Growth PDF
Preview Regulation of Organ and Tissue Growth
CONTRIBUTORS Donald Bartlelt, Jr. Bryant Benson R. R. Burton Sidney R. Cooperband Patrick J. Fitzgerald Richard J. Goss Ludmila Grauel Lloyd Guth C. P. Leblond Bernard Lytton Edwin A. Mir and Melvin L. Moss T. T. Odell, Jr. Richard J. Orts Charlotte A. Schneyer Bernard Sigel Anna Steinberger Emil Steinberger Doris M. Stewart M. David Tilson Edith van Marthens Hastings K. Wright Stephen Zamenhof Regulation of Organ and Tissue Growth Edited by RICHARD J. GOSS Division of Biological and Medical Sciences Broivn University, Providence, Rhode Island ACADEMIC PRESS 1972 New York and London COPYRIGHT © 1972, BY ACADEMIC PRESS, INC. ALL RIGHTS RESERVED. NO PART OF THIS PUBLICATION MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM OR BY ANY MEANS, ELECTRONIC OR MECHANICAL, INCLUDING PHOTOCOPY, RECORDING, OR ANY INFORMATION STORAGE AND RETRIEVAL SYSTEM, WITHOUT PERMISSION IN WRITING FROM THE PUBLISHER. ACADEMIC PRESS, INC. Ill Fifth Avenue, New York, New York 10003 United Kingdom Edition published by ACADEMIC PRESS, INC. (LONDON) LTD. 24/28 Oval Road, London NW1 LIBRARY OF CONGRESS CATALOG CARD NUMBER: 72-82627 PRINTED IN THE UNITED STATES OF AMERICA LIST OF CONTRIBUTORS Numbers in parentheses indicate the pages on which the authors' contributions begin. DONALD BARTLETT, JR. (197), Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire BRYANT BENSON (315), Department of Anatomy, University of Texas Medical Branch, Galveston, Texas R. R. BURTON (101), Biodynamics Branch (SMB), USAF School of Aero space Medicine, Brooks Air Force Base, Texas SIDNEY R. cooPERBAND (159), Department of Medicine and Microbiology, Boston University School of Medicine, Boston, Massachusetts PATRICK j. FITZGERALD* (233), Department of Pathology, Downstate Medical Center, State University of New York, Brooklyn, New York RICHARD j. Goss (J, 337), Division of Biological and Medical Sciences, Brown University, Providence, Rhode Is^d LUDMiLA GRAUEL (41), Department of Psychiatry, Neuropsychiatrie Institute, University of California, Los Angeles, California LLOYD GUTH (61), National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland c. P. LEBLOND (13), Department of Anatomy, McGill University, Montreal, Canada BERNARD LYTTON (283), Department of Urology, Yale University School of Medicine, New Haven, Connecticut * Present address: Department of Pathology, Sloan-Kettering Institute for Cancer Research, New York, New York. xi xii List of Contributors EDWIN A. MiRAND (143), Rosiceli Park Memorial Institute, Neio York State Department of Health, Buffalo, New York MELViN L. MOSS (127), Department of Anatomy, College of Physicians and Surgeons, Columbia University, Neio York, New York T. T. ODELL, JR. (187), Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee RICHARD j. ORTS (315), Department of Anatomy, University of Texas Medical Branch, Galveston, Texas CHARLOTTE A. scHNEYER (211), Department of Physiology and Biophysics, University of Alabama Medical Center, Birmingham, Alabama BERNARD SIGEL (271), Departments of Surgery and Pathology, Medical College of Pennsylvania, Philadelphia, Pennsylvania ANNA STEINBERGER (299), Program in Reproductive Biology and Endo crinology, University of Texas Medical School at Houston, Houston, Texas EMIL STEINBERGER (299), Program in Reproductive Biology and Endo crinology, University of Texas Medical School at Houston, Houston, Texas DORIS M. STEWART (77), Department of Biology, Central Michigan University, Mount Pleasant, Michigan M. DAVID TILSON (257), Department of Surgery, Yale University School of Medicine, New Haven, Connecticut EDITH VAN MARTHENS (41), Department of Psychiatry, Neuropsychiatrie Institute, University of California, Los Angeles, California HASTING K. WRIGHT (257), Department of Surgery, Yale University School of Medicine, New Haven, Connecticut STEPHEN ZAMENHOF (41), Department of Medical Microbiology and Immunology, Department of Biological Chemistry, Brain Research Institute, and Mental Retardation Center, University of California School of Medicine, Los Angeles, California PREFACE Ideas resemble soil—unless turned over from time to time nothing new will come to the surface. They will become hard packed and brit tle, and may eventually turn into fossils. There is no dearth of potential ideas in the field of growth regulation. This volume has plowed up some good ones; it has also buried a few. The symposium from which this book developed was held in Philadelphia on December 29 and 30, 1971, under the auspices of the American Association for the Advancement of Science. Comprised of contributors from a wide spectrum of fields, it sought to encourage an exchange of ideas among people whose paths do not ordinarily cross. A scientist who does not know how others have solved problems similar to his own is comparable to a person who has never appreciated the benefits of travel. He may become dangerously provincial, and thinking he knows the answer may barely understand the question. How the multitude of tissues and organs with which we are endowed attain just the right size in relation to each other is the problem. With the possible exception of cancer, these diverse expressions of growth have one thing in common—their rates are very carefully regulated. Something triggers the onset of growth, sustains it for a finite period, determines its magnitude, and stops it when enough new tissue has been produced. The nature of these elusive regulatory influences has been the subject of debate for many years. Much of the controversy has arisen because each of us in the field of growth regulation naturally gravitates toward one or another of our favorite organs or tissues as an object of study. To the extent that our attention is focused on a chosen organ, other systems tend to be neglected, and with them perhaps the answers to our questions. Just as it is necessary to compare the different tissues, it is important to understand how different kinds of growth are related irrespective of the tissues in which they may be expressed. Does the compensatory xiii XIV Preface growth of overworked organs or of their remnants following reductions in mass differ in quality, or just in degree, from the ontogenetic growth of normal development? Is the renewal of tissues which offsets the losses of turnover equivalent to that which follows injury? Could the negative growth of disuse atrophy explain pathological dystrophies or the tissue depreciations of growing old? The answers to these questions will not, unfortunately, be found in the chapters that follow. They may never be found unless we start worry ing about fundamentals. The discerning reader will realize that it is not so important to discover how growth is regulated in this tissue or that organ for its own sake. Each case helps to solve the puzzle of growth, and only if we look for emerging patterns may we eventually see "the forest for the trees." Richard J. Goss CHAPTER 1 THEORIES OF GROWTH REGULATION Richard J. Goss I. Introduction 1 II. Self-Inhibition 2 III. Exogenous Stimulation 3 IV. Functional Demands 5 V. Systemic versus Local Control 7 VI. Conclusions 9 References 10 1. Introduction Hypotheses abound as to how growth is regulated in organs and tissues. None, however, is universally accepted. Most do not deserve to be. To propose a hypothesis is to invite the slings and arrows of waiting critics. If it is an honest hypothesis, it is one that can be put to the test, which means that sooner or later someone will probably prove it wrong. Yet in the wake of its demise there often remains a wealth of new infor mation that might not have been sought had there been no hypothe sis to challenge in the first place. Such is the debt of gratitude owed to those who have had the courage to venture beyond the safety of estab lished fact. Without their inspiration, many a crucial experiment might never have been performed. Existing hypotheses of growth regulation can be categorized in several ways. Some propose the operation of inhibitors; others propose 1 2 RICHARD J. GOSS stimulators. Some would have each organ and tissue control its own growth. Others put the regulator elsewhere in the body. There may be a single site that orchestrates the growth of everything else, or as many different control centers as there are parts of the body to be governed. Some theories have been formulated to explain the growth of a specific organ or tissue; others encompass the entire histological spectrum. The problem is to bring some order to this bewildering profusion of hypotheses. There are two schools of thought to explain the orderly growth of organs and tissues. One contends that the dimensions of body parts are genetically predetermined. The other holds that the correct size of an organ is a function of the physiological demands impinging on it. The pros and cons of whether size controls function, or vice versa, have been reviewed by a number of authors, notably Warburton (1955), Aber- crombie (1957), S wann (1958), Paschkis (1958), Goss (1964), and Bucherand Malt (1971). From the phylogenetic point of view, the allometric growth of each organ is, of course, adapted to the needs of the organism. These genetic adaptations have been shaped by natural selection and are independent of the short-term vicissitudes of the environment. Physiological adapta tions on the other hand are responsible for the fluctuations in organ weights that reflect increases or decreases in functional demands. These two adaptations work together like the coarse and fine adjustments in focusing a microscope. Inheritance assures that each given organ will be present regardless of whether it is needed or not. The rate of physio logical activity, on the other hand, regulates the size to which it will grow over and above the genetically predetermined minimum. So it is that, even under conditions of Lotal disuse, most tissues atrophy, but do not disappear altogether. II. Self-Inhibition Ultimately, it is important to explain the growth of organs and tissues in terms of specific regulatory substances, irrespective of the afore mentioned genetic and physiological aspects of the problem. A number of investigators have suggested that growth may be controlled by negative feedback mechanisms involving the operation of specific inhibitors pro duced by the tissue whose growth is to be controlled. Weiss (1955), Weiss and Kavanau (1957), and Kavanau (1960) formulated a particularly interesting hypothesis to explain organ growth in terms of self-inhibition. According to this, each organ produces growth inhibitors that are released into the extracellular body fluids. These in- 1. Theories of Growth Regulation 3 hibitors, or antitemplates, diffuse back and forth across cell membranes and are capable of interacting with complementary templates within the cell. The templates normally stimulate cell growth, but cannot do so when bound to their corresponding antitemplates. Thus, growth occurs whenever the number of templates in the cell exceeds the number of antitemplates, the latter being in equilibrium with the extracellular population. Hence, a growing organ will produce an increasing number of antitemplate inhibitors in the circulation until such time as their con centration builds up to the point where they inactivate all the tem plates. If the mass of a given organ is reduced, then the concentration of inhibitors falls off and compensatoiy growth is turned on. Needless to say, this ingenious theory has prompted considerable research in the field of organ growth regulation. Along these same lines, Rose (1957) suggested that during develop ment each tissue might inhibit its own growth when an appropriate mass had been attained. Bullough ( 1964, 1965 ) advanced a similar idea which grew out of his research on the regulation of cell turnover in the epi dermis. According to this hypothesis, epidermal cells produce substances called chalones that inhibit the mitotic activity of the basal layer of germinative cells in the epidermis. The ideas of Weiss, Rose, and Bullough all have much in common in that their principal regulatory substances are inhibitors, and that they are produced by the organs whose growth they control. They imply that cellular proliferation is not subject to exogenous stimulators, but that tissues have an innate tendency to grow and can therefore be controlled solely by inhibitory compounds—like controlling the velocity of an auto mobile by using the brakes instead of the accelerator. 111. Exogenous Stimulation Still another hypothesis has been proposed by Tanner (1963) to explain overall body growth in terms of both inhibitors and stimulators. According to this, the body produces inhibitors that are monitored by a control center outside the organs being controlled. Since in the course of normal ontogeny the brain develops earlier than any other part of the body, Tanner suggests that it might be a likely site of growth regulation. Thus, the brain may constantly compare the actual size of the body with the size it should be at any given age and produce growth stimulators in proportion to the discrepancy detected. A somewhat similar hypothesis, this one advanced by Burwell (1963), Burch and Burwell (1965), and Burch (1969), likewise contends that one kind of tissue regulates the growth of all others. In this case, it is
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