Neuroendocrinology of Aging Neuroendocrinology of Aging Edited by Joseph Meites Michigan State University East Lansing, Michigan Plenum Press • New York and London Library of Congress Cataloging in Publication Data Main entry under title: Neuroendocrinology of aging. Includes bibliographical references and index. 1. Neuroendocrinology. 2. Aging. 3. Endocrine glands-Diseases-Age factors. I. Meites, Joseph, 1913- . [DNLM: 1. Endocrine glands-Physiology. 2. Nervous system-Physiology. WK 102 N4935] OP356.4.N4835 1983 599'.0188 83-10937 ISBN-13: 978-1-4684-4525-1 e-ISBN-13: 978-1-4684-4523-7 001: 10.1007/978-1-4684-4523-7 © 1983 Plenum Press, New York A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Contributors Pierre Aschheim, Unite de Recherches Gerontologiques, INSERM U.118, 75016 Paris, France Charles F. Aylsworth, Department of Anatomy, Michigan State Uni versity, East Lansing, Michigan 48824 James A. Clemens, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285 Julian M. Davidson, Department of Physiology, Stanford University, Stanford, California 94305 Caleb E. Finch, Andrus Gerontology Center, Department of Biological Sciences, University of Southern California, Los Angeles, California 90007 Lloyd J. Forman, Department of Medicine, University of Medicine and Dentistry of New Jersey, Camden, New Jersey 08103 Paul E. Gottschall, Department of Physiology, Neuroendocrine Re search Laboratory, Michigan State University, East Lansing, Mich igan 48824 Gary D. Gray, Department of Physiology, Stanford University, Stanford, California 94305 Robert I. Gregerman, Gerontology Research Center, National Institute on Aging, NIH, Baltimore City Hospital, Baltimore, Maryland 21224 S. Mitchell Harman, Endocrinology Section, Clinical Physiology Branch, Gerontology Research Center, Kational Institute on Aging, NIH, Baltimore City Hospital, Baltimore, Maryland 21224 Henry H. H. Huang, Research Laboratory, Mercy Hospital and Medical Center, Chicago, Illinois 60616 Howard L. Judd, Department of Obstetrics and Gynecology, University of California at Los Angeles School of Medicine, Los Angeles, Cal ifornia 90024 v vi CONTRIBUTORS John K. H. Lu, Departments of Obstetrics/Gynecology and Anatomy, University of California at Los Angeles School of Medicine, Los Angeles, California 90024 Joseph Meites, Department of Physiology, Neuroendocrine Research Laboratory, Michigan State University, East Lansing, Michigan 48824 Charles V. Mobbs, Andrus Gerontology Center, Department of Bio logical Sciences, University of Southern California, Los Angeles, California 90007 Ming-Tsung Peng, Department of Physiology, National Taiwan Uni versity Medical School, Taipei, Taiwan Gail D. Riegle, Department of Physiology, Michigan State University, East Lansing, Michigan 48824 Dipak K. Sarkar, Department of Reproductive Medicine, University of California, San Diego, California 92093 James W. Simpkins, Department of Pharmaceutical Biology, College of Pharmacy, University of Florida, Gainesville, Florida 32610 Erla R. Smith, Department of Physiology, Stanford University, Stanford, California 94305 William E. Sonntag, Department of Physiology, Neuroendocrine Re search Laboratory, Michigan State University, East Lansing, Mich igan 48824 Richard W. Steger, Department of Obstetrics and Gynecology, Univer sity of Texas Health Science Center at San Antonio, San Antonio, Texas 78284 Paola S. Timiras, Department of Physiology-Anatomy, University of California, Berkeley, California 94720 Clifford W. Welsch, Department of Anatomy, Michigan State University, East Lansing, Michigan 48824 Contents Chapter 1 Introduction Joseph Meites Chapter 2 Neuroendocrinology of Aging: Retrospective, Current, and Prospective Views Paola S. Timiras 1. Introduction............................................. 5 2. Retrospection............................................ 6 3. Current Neuroendocrine Theories of Aging ................ 9 3.1. The Hypothalamic "Disregulation" Hypotheses. . . . . . . . . 9 3.2. The Neurotransmitter Hypotheses .................... 13 3.3. The Pituitary Hypotheses ............................ 16 3.4. Progeria and Progeroid Syndromes ................... 18 3.5. The Stress Theory of Aging. . . . . . . . . . . . . . . . . . . . . . . . .. 18 4. Outlook ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20 4.1. Refinement in Detection of Neuroendocrine Changes with Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 21 4.2. Comparative Aspects of Neuroendocrine Changes with Aging .............................................. 21 4.3. Relations between Neuroendocrine and Immune Controls in Aging ................................... 22 4.4. Molecular Biology of Brain Hormones and of Hormonal Actions on Brain .................................... 23 vII vIII CONTENTS 4.5. Changes with Aging in Hormone Metabolism and Tissue Responses .................................... 23 4.6. Oxidative Cell Damage with Aging and Actions of Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 24 5. Summary and Conclusions ................................ 25 6. References............................................... 25 Chapter 3 Morphological Changes in the Hypothalamus and Other Brain Areas Influencing Endocrine Function during Aging James A. Clemens 1. Introduction............................................. 31 2. Nerve Cell Loss .......................................... 31 3. Other Morphological Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 33 4. Hormones as Causative Factors in the Neuronal Degenerative Processes. . . . . . . . . . . . . . . . . . . . . .. 34 4.1. Estrogens, Prolactin, and the Arcuate Nucleus. . . . . . . . .. 34 4.2. Glucocorticoids and the Hippocampus. . . . . . . . . . . . . . . .. 35 4.3. Estrogens, Prolactin, and Nigrostriatal Neurons ........ 35 5. Brain Lesions That Mimic Age-Related Changes ............ 36 6. Biochemical Evidence for Age-Induced Morphological Changes ................................... 36 7. General Summary. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .. 37 8. References............................................... 37 Chapter 4 Changes in Hypothalamic Hypophysiotropic Hormones and Neurotransmitters during Aging James W. Simpkins 1. Introduction ............................................. 41 2. Aging of Dopaminergic Neurons .......................... 42 3. Aging of Noradrenergic Neurons. . . . . . . . . . . . . . . . . . . . . . . . .. 45 4. Aging of Serotonergic Neurons. . . . . . . . . . . . . . . . . . . . . . . . . . .. 47 5. Aging of Opioid Neurons. . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 48 CONTENTS Ix 6. Aging of Luteinizing Hormone-Releasing Hormone (LHRH) Neurons ........................................ 49 7. Aging of Somatostatin Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . .. 51 8. Aging of Thyrotropin-Releasing-Hormone Neurons ......... 51 9. Summary ................................................ 52 10. References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 53 Chapter 5 Changes in Hormone Uptake and Receptors in the Hypothalamus during Aging Ming-Tsung Peng 1. Introduction............................................. 61 2. Sex Steroid Uptake and Receptor Binding in the Hypothalamus during Aging .............................. 62 2.1. Estrogen Receptor Binding ........................... 62 2.2. Androgen Receptor Binding. . . . . . . . . . . . . . . . . . . . . . . . .. 66 2.3. Relation between Changes in Sex Steroid Uptake in the Hypothalamus and Changes in Feedback Response to Sex Steroids during Aging. . . . . . . . . . . . . . . . . . . . . . . . . . .. 66 2.4. Relation between Changes in Sex Steroid Binding to Receptors in the Hypothalamus and Changes in Hypothalamic Neuronal Numbers during Aging. . . . . . .. 67 3. Corticosteroid Uptake and Binding to Receptors in the Hypothalamus during Aging .............................. 68 4. Summary................................................ 70 5. References............................................... 70 Chapter 6 Relation of Neuroendocrine System to Reproductive Decline in Female Rats Pierre Aschheim 1. Introduction............................................. 73 2. Preliminary Comments on Hormonal Data in Old Rats ...... 74 3. Relation of Neuroendocrine System to Ovarian Function after the End of Cyclicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 78 3.1. Senile Patterns of Ovarian Function. . . . . . . . . . . . . . . . . .. 78 x CONTENTS 3.2. Aging of the Neuroendocrine Regulation of Ovarian Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 83 4. Relation of Neuroendocrine System to Ovarian Function during Cyclicity and Transition Period ..................... 87 4.1. Aging of Ovarian Function during Cyclicity: Physiological and Structural Changes ..... . . . . . . . . . . . .. 87 4.2. Aging of the Neuroendocrine Regulation of Cyclic Ovarian Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 89 5. Experimental Manipulations of H ypothalamic-Hypophysial-Ovarian Aging.. . . . . . . . . . . . . . . . .. 91 5.1. Suspended Aging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 91 5.2. Retarded Aging ..................................... 93 5.3. Advanced Aging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 94 6. Extrinsic and Intrinsic Aging .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 94 7. Conclusions.............................................. 96 8. References............................................... 97 Chapter 7 Changes in Ovarian Function and Gonadotropin and Prolactin Secretion in Aging Female Rats John K. H. Lu 1. Introduction ............................................. 103 2. Changes in Ovarian Function .............................. 104 3. Changes in Gonadotropin Secretion ........................ 109 4. Changes in Prolactin Secretion ............................. 115 5. Alterations in Ovarian Steroid and Periovulatory Gonadotropin Secretion Preceding Cessation of Regular Estrous Cycles .................................... 117 6. Conclusions .............................................. 119 7. References ............................................... 120 Chapter 8 The Reproductive Decline in Male Rats Richard W. Steger and Henry H. H. Huang 1. Introduction ............................................. 123 2. Testicular Structure and Function ......................... 123