Table Of ContentNeuroendocrinology
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
