Relation of Neuroendocrine System to Reproductive Decline in Female Rats

  • Pierre Aschheim


The reproductive decline in female mammals is universal. Age-related sterility in rats is complete at about 15–17 months (Miller et al., 1979), when approximately 50–60% of the lifetime is spent. This type of sterility is multifactorial, the most important factor being senescence of the uterus. Oocyte alterations also occur. Disregarding these reproductive aspects, we will focus on aging of the hypothalamic-hypophysialovarian axis.


Luteinizing Hormone Estrous Cycle Luteinizing Hormone Surge Luteinizing Hormone Secretion Luteinizing Hormone Release 


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  1. Aschheim, P., 1961, La pseudogestation à répétition chez les rattes séniles, C. R. Acad. Sci. 253: 1988–1990.Google Scholar
  2. Aschheim, P., 1964/5, Résultats fournis par la greffe hétérochrone des ovaires dans l’étude de la régulation hypothalamo-hypophyso-ovarienne de la ratte sénile, Gèrontologia 10: 65–75.PubMedCrossRefGoogle Scholar
  3. Aschheim, P., 1965, La réactivation de l’ovaire des rattes séniles en oestrus permanent au moyen d’hormones gonadotropes ou de la mise à l’obscurité, C. R. Acad. Sci. 260: 5627–5630.Google Scholar
  4. Aschheim, P., 1968, Contenu hypophysaire en hormone lutéinisante (LH) et réaction histophysiologique à la LH circulante du tissu interstitiel ovarien chez divers types de rattes séniles, C. R. Acad. Sci. 267: 1397–1400.Google Scholar
  5. Aschheim, P., 1970, La rétroaction ovarienne dans la régulation hypothalamique de la fonction gonadotrope LH de la ratte sénile, in: Colloques Nationaux du CNRS, n° 927: Neuroendocrinologie U. Benoit and C. Kordon, eds.), CNRS, Paris, pp. 363–376.Google Scholar
  6. Aschheim, P., 1974, A biological aging test for the hypothalamo-hypophyseal regulation of the estrous cycle in the rat, in: Endocrinology of Sex. Differentiation and Neuroendocrine Regulation in the Hypothalamo-Hypophyseal-Gonadal System ( G. Dörner, ed.), J. A. Barth, Leipzig, pp. 352–358.Google Scholar
  7. Aschheim, P., 1975, Effets de l’administration chronique de stéroides anticonceptionnels sur l’âge biologique des cycles ovariens de la ratte après arrêt du traitement, Ann. Biol. Anim. 15: 775–783.CrossRefGoogle Scholar
  8. Aschheim, P., 1976, Aging in the hypothalamic-hypophyseal ovarian axis in the rat, in: Hypothalamus, Pituitary and Aging ( A. V. Everitt and J. A. Burgess, eds.), Ch. C. Thomas, Springfield, pp. 376–418.Google Scholar
  9. Aschheim, P., 1979, Function of the aging ovary: Comparative aspects, Eur. J. Obstet. Gynecol. Reprod. Biol. 9: 191–202.Google Scholar
  10. Aschheim, P., 1982, Deux modèles opposés du vieillissement de l’ovaire et de sa commande hypothalamo-hypophysaire: la ratte et la souris CBA, Sci. Techn. Anim. Lab. 7: 99–108.Google Scholar
  11. Aschheim, P., and Latouche, J., 1975, Les effets du séjour au froid sur le cycle ovarien de la ratte et son âge biologique, in: Problèmes Actuels d’Endocrinologie ( H. P. Klotz, ed.), Exp. Sci. Fr., Paris, pp. 95–110.Google Scholar
  12. Aschheim, P., and Pasteels, J. L., 1963, Etude histophysiologique de la sécrétion de prolactine chez les rattes séniles, C. R. Acad. Sci. 257: 1373–1375.Google Scholar
  13. Aschheim, P., and Rasolonjanahary, R., 1979, Age-dependency of pituitary prolactin secretion in vitro and of its sensitivity to estrogen in rats, in: Recent Advances in Gerontology ( H. Ozimo, K. Shimada, M. Iriki, and D. Maeda, eds.), Excerpta Medica, Amsterdam, pp. 481–484.Google Scholar
  14. Barnea, A., Cho, G., and Porter, J. C., 1980, Effect of aging on the subneuronal distribution of luteinizing hormone-releasing hormone in the hypothalamus, Endocrinology 106: 1980–1988.PubMedCrossRefGoogle Scholar
  15. Brawer, J. R., Schipper, H., and Naftolin, F., 1980, Ovary-dependent degeneration in the hypothalamic arcuate nucleus, Endocrinology 107: 274–279.PubMedCrossRefGoogle Scholar
  16. Butcher, R. L., and Page, R. D., 1981, Role of the aging ovary in cessation of reproduction, in: Dynamics of Ovarian Function ( N. B. Schwartz and M. Hunzicker-Dunn, eds.), Raven Press, New York, pp. 253–271.Google Scholar
  17. Clemens, J. A., 1979, CNS as a pacemaker of endocrine dysfunction in aging and its pharmacological intervention by lergotrile mesylate, in: Interdiscipl. Topics Gerontol., Vol. 15 ( H. P. von Hahn, ed.), S. Karger, Basel, pp. 77–84.Google Scholar
  18. Clemens, J. A., and Meites, J., 1971, Neuroendocrine status of old constant-estrous rats, Neuroendocrinology 7: 249–256.PubMedCrossRefGoogle Scholar
  19. Conn, P. M., Cooper, R., McNamara, C., Rogers, D. C., and Shoenhardt, L., 1980, Qualitative change in gonadotropin during normal aging in the male rat, Endocrinology 106: 1549–1553.PubMedCrossRefGoogle Scholar
  20. Cooper, R. L., and Walker, R. F., 1979, Potential therapeutic consequences of age-dependent changes in brain physiology, in: Interdiscipl. Topics Gerontol., Vol. 15 ( H. P. von Hahn, ed.), S. Karger, Basel, pp. 54–76.Google Scholar
  21. Cooper, R. L., Conn, P. M., and Walker, R. F., 1980, Characterization of the LH surge in middle-aged female rats, Biol. Reprod. 23: 611–615.PubMedCrossRefGoogle Scholar
  22. Crumeyrolle-Arias, M., 1979, In vivo aging of rat’s ovarian interstitial cells made nondividing through hypophysectomy, Gerontology 25: 162.Google Scholar
  23. Crumeyrolle-Arias, M., and Aschheim, P., 1981, Post-hypophysectomy ovarian senescence and its relation to the spontaneous structural changes in the ovary of intact aged rats, Gerontology 27: 58–71.PubMedCrossRefGoogle Scholar
  24. Crumeyrolle-Arias, M., Scheib, D., and Aschheim, P., 1976, Light and electron microscopy of the ovarian interstitial tissue in the senile rat: Normal aspect and response to HCG of “Deficiency Cells” and “Epithelial Cords,” Gerontology 22: 185–204.PubMedCrossRefGoogle Scholar
  25. Damassa, D. A., Gilman, D. P., Lu, K. H., Judd, H. L., and Sawyer, C. H., 1980, The twenty-four hour pattern of prolactin secretion in aging female rats, Biol. Reprod. 22: 571–575.PubMedGoogle Scholar
  26. Elias, K. A., Huffman, L. J., and Blake, C. A., 1979, Age of ovariectomy affects subsequent plasma LH responses in old age rats, Program of the 61 st Annual Meeting of the Endocrine Society, Anaheim, California (Abst. 133 ), p. 106.Google Scholar
  27. Erickson, G. F., Hsueh, A.J. W., and Lu, K. H., 1979, Gonadotropin binding and aromatase activity in granulosa cells of young proestrous and old constant estrous rats, Biol. Reprod. 20: 182–190.PubMedCrossRefGoogle Scholar
  28. Estes, K. S., Simpkins, J. W., and Chen, C. L., 1980, Alteration in pulsatile release of LH in aging female rats, Proc. Soc. Exp. Biol. Med. 163: 384–387.PubMedGoogle Scholar
  29. Everett, J. W., 1980, Reinstatement of estrous cycles in middle-aged spontaneously persistent estrous rats: Importance of circulating prolactin and the resulting facilitative action of progesterone, Endocrinology 106: 1691–1696.PubMedCrossRefGoogle Scholar
  30. Fayein, N. A., and Aschheim, P., 1980, Age-related temporal changes of levels of circulating progesterone in repeatedly pseudopregnant rats, Biol. Reprod. 23: 616–620.PubMedCrossRefGoogle Scholar
  31. Fugo, N. W., and Butcher, R. L., 1971, Effects of prolonged estrous cycles on reproduction in aged rats, Fertil. Steril. 22: 98–101.PubMedGoogle Scholar
  32. Germain, B. J., Campbell, P. S., and Anderson, J. N., 1978, Role of the serum estrogen-binding protein in the control of tissue estradiol levels during postnatal development of the female rat, Endocrinology 103: 1401–1410.PubMedCrossRefGoogle Scholar
  33. Gilman, D. P., Lu, K. H., Whitmoyer, D. I., Judd, H. L., and Sawyer, C. H., 1981, Relationship between progesterone and prolactin surges in aged and young pseudopregnant rats, Biol. Reprod. 24: 839–845.PubMedCrossRefGoogle Scholar
  34. Gosden, R. G., and Bancroft, L., 1976, Pituitary function in reproductively senescent female rats, Exp. Gerontol. 11: 157–160.PubMedCrossRefGoogle Scholar
  35. Grandison, L., Hodson, C., Chen, H. T., Advis, J., Simpkins, J., and Meites, J., 1977, Inhibition by prolactin of post-castration rise in LH, Neuroendocrinology 23: 312–322.PubMedCrossRefGoogle Scholar
  36. Gray, G. D., and Wexler, B. C., 1980, Estrogen and testosterone sensitivity of middle-aged female rats in the regulation of LH, Exp. Gerontol. 15: 201–207.PubMedCrossRefGoogle Scholar
  37. Gray, G. D., Tennent, B., Smith, E. R., and Davidson, J. M., 1980, Luteinizing hormone regulation and sexual behavior in middle-aged female rats, Endocrinology 107: 187–194.PubMedCrossRefGoogle Scholar
  38. Howland, B. E., 1976, Reduced gonadotropin release in response to progesterone or gonadotropin releasing hormone (GnRH) in old female rats, Life Sci. 19: 219–224.PubMedCrossRefGoogle Scholar
  39. Hsu, H. K., and Peng, M. T., 1978, Hypothalamic neuron number of old female rats, Gerontology 24: 434–440.PubMedCrossRefGoogle Scholar
  40. Huang, H. H., Marshall, S., and Meites, J., 1976a, Capacity of old versus young female rats to secrete LH, FSH and prolactin, Biol. Reprod. 14: 538–543.PubMedCrossRefGoogle Scholar
  41. Huang, H. H., Marshall, S., and Meites, J., 1976b, Induction of estrous cycles in old noncyclic rats by progesterone, ACTH, ether stress or L-Dopa, Neuroendocrinology 20: 21–34.PubMedCrossRefGoogle Scholar
  42. Huang, H. H., Steger, R. W., Bruni, J. F., and Meites, J., 1978, Patterns of sex steroid and gonadotropin secretion in aging female rats, Endocrinology 103: 1855–1859.PubMedCrossRefGoogle Scholar
  43. Huang, H. H., Simpkins, J., and Meites, J., 1979, Hypothalamic norepinephrine and dopamine turnover in ovariectomized old rats treated with gonadal steroids, Physiologist (Abst.) 22: 71.Google Scholar
  44. Huang, H. H., Steger, R. W., Sonntag, W. E., and Meites, J., 1980, Positive feedback by ovarian hormones on prolactin and LH in old versus young female rats, Neurobiol. Aging 1: 141–143.CrossRefGoogle Scholar
  45. Jiang, M. J., and Peng, M. T., 1981, Cytoplasmic and nuclear binding of estradiol in the brain and pituitary of old female rats, Gerontology 27: 51–57.PubMedCrossRefGoogle Scholar
  46. Jones, E. C., and Krohn, P. L., 1961, The effect of hypophysectomy on age changes in the ovaries of mice, J. Endocrinol. 27: 497–509.CrossRefGoogle Scholar
  47. Kaler, L. W., and Neaves, W. B., 1981, The androgen status of aging male rats, Endocrinology 108: 712–719.PubMedCrossRefGoogle Scholar
  48. Kawashima, S., 1974, Morphology and function of prolactin cells in old female rats, Gumma Symp. Endocrinol. 11: 129–141.Google Scholar
  49. Kovacs, K., Horvath, E., Ilse, R. G., Ezrin, C., and Ilse, D., 1977, Spontaneous pituitary adenomas in aging rats. A light microscopic, immunocytological and fine structural study, Beitr. Pathol. 161: 1–16.PubMedCrossRefGoogle Scholar
  50. Lin, K. H., Peng, Y. M., Peng, M. T., and Tseng, T. M., 1976, Changes in the nuclear volume of rat hypothalamic neurons in old age, Neuroendocrinology 21: 247–254.PubMedCrossRefGoogle Scholar
  51. Linnoila, M., and Cooper, R. L., 1976, Reinstatement of vaginal cycles in aged female rats, J. Pharmacol. Exp. Ther. 199: 477–482.PubMedGoogle Scholar
  52. Lu, J. K. H., and Kledzik, G. S., 1981, Chronological changes in ovarian function and morphology in aging rats and their relation to neuroendocrine responses, in: Dynamics of Ovarian Function ( N. B. Schwartz and M. Hunzicker-Dunn, eds.), Raven Press, New York, pp. 291–296.Google Scholar
  53. Lu, K. H., Huang, H. H., Chen, H. T., Kurcz, M., Mioduszewski, R., and Meites, J., 1977, Positive feed-back by estrogen and progesterone on LH release in old and young rats, Proc. Soc. Exp. Biol. Med. 154: 82–85.PubMedGoogle Scholar
  54. Lu, K. H., Hopper, B. R., Vargo, T. M., and Yen, S. S. C., 1979, Chronological changes in sex steroid, gonadotropin and prolactin secretion in aging female rats displaying different reproductive states, Biol. Reprod. 21: 193–203.PubMedCrossRefGoogle Scholar
  55. Lu, J. K. H., Damassa, D. A., Gilman, D. P., Judd, H. L., and Sawyer, C. H., 1980, Differential patterns of gonadotropin responses to ovarian steroids and to LH-releasing hormone between constant-estrous and pseudopregnant states in aging rats, Biol. Reprod. 23: 345–351.PubMedCrossRefGoogle Scholar
  56. Lu, J. K. H., Gilman, D. P., Meldrum, D. R., Judd, H. L., and Sawyer, C. H., 1981, Relationship between circulating estrogens and the central mechanisms by which ovarian steroids stimulate luteinizing hormone secretion in aged and young female rats, Endocrinology 108: 836–841.PubMedCrossRefGoogle Scholar
  57. Mandl, A. M., and Zuckerman, S., 1951, The relation of age to numbers of oocytes, J. Endocrinol. 7: 190–193.PubMedCrossRefGoogle Scholar
  58. McPherson, J. C., Costoff, A., and Mahesh, V. B., 1977, Effects of aging on the hypothalamic-hypophyseal-gonadal axis in female rats, Fertil. Steril. 28: 1365–1370.PubMedGoogle Scholar
  59. Meites, J., Huang, H. H., and Simpkins, J. W., 1978, Recent studies on neuroendocrine control of reproductive sensecence in rats, in: The Aging Reproductive System ( E. L. Schneider, ed.), Raven Press, New York, pp. 213–235.Google Scholar
  60. Meites, J., Simpkins, J. W., and Huang, H. H., 1979, The relation of hypothalamic biogenic amines to secretion of gonadotropins and prolactin in the aging rat, in: Physiology and Cell Biology of Aging (A. Cherkin et al.,eds.), Raven Press, New York, pp. 87–94.Google Scholar
  61. Merchenthaler, I., Lengvhri, I., Horvath, J., and Sétaló, G., 1980, Immunohistochemical study of the LHRH-synthesizing neuron system of aged female rats, Cell Tissue Res. 209: 499–503.PubMedCrossRefGoogle Scholar
  62. Merry, B. J., and Holehan, A. M., 1979, Onset of puberty and duration of fertility in rats fed a restricted diet, J. Reprod. Fertil. 57: 253–259.PubMedCrossRefGoogle Scholar
  63. Miller, A. E., Wood, S. M., and Riegle, G. D., 1979, The effect of age on reproduction in repeatedly mated female rats, J. Gerontol. 34: 15–20.PubMedGoogle Scholar
  64. Parkening, T. A., Collins, T. J., and Smith, E. R., 1980a, A comparative study of prolactin levels in five species of aged female laboratory rodents, Biol. Reprod. 22: 513–518.PubMedCrossRefGoogle Scholar
  65. Parkening, T. A., Collins, T. J., and Smith, E. R., 1980b, Plasma and pituitary concentrations of LH, FSH and prolactin in aged female C57 BL/6 mice, J. Reprod. Fertil. 58: 377–386.PubMedCrossRefGoogle Scholar
  66. Peluso, J. J., and England-Charlesworth, C., 1981, Formation of ovarian cysts in aged irregularly cycling rats, Biol. Reprod. 24: 1183–1190.PubMedGoogle Scholar
  67. Peluso, J. J., Steger, R. W., and Hafer, E. S. E., 1977, Regulation of LH secretion in aged female rats, Biol. Reprod. 16: 212–215.PubMedCrossRefGoogle Scholar
  68. Peluso, J. J., Steger, R. W., Huang, H. H., and Meites, J., 1979, Pattern of follicular growth and steroidogenesis in the ovary of aging cycling rats, Exp. Aging Res. 5: 319–333.PubMedCrossRefGoogle Scholar
  69. Peluso, J. J., Hutz, R., and England-Charlesworth, C., 1981, Age-related alterations in preovulatory oocytes, in: Dynamics of Ovarian Function ( N. B. Schwartz and M. Hunzicker Dunn, eds.), Raven Press, New York, pp. 303–308.Google Scholar
  70. Peng, M. T., and Huang, H. H., 1972, Aging of hypothalamic-pituitary-ovarian function in the rat, Fertil. Steril. 23: 535–542.PubMedGoogle Scholar
  71. Peng, M. T., and Peng, Y. M., 1973, Changes in the uptake of tritiated estradiol in the hypothalamus and adenohypophysis of old female rats, Fertil. Steril. 24: 534–539.PubMedGoogle Scholar
  72. Rasolonjanahary, R., 1979, Evolution, en fonction de l’âge, de la sécrétion de prolactine hypophysaire in vitro chez le rat. Effet de l’oestradiol et de la dopamine, Physiology of Reproduction, Sc.D. Dissertation, Université Pierre et Marie Curie, Paris 6.Google Scholar
  73. Riegle, G. D., and Miller, A. E., 1978, Aging effects on the hypothalamic-hypophysealgonadal control system in the rat, in: The Aging Reproductive System ( E. L. Schneider, ed.), Raven Press, New York, pp. 159–192.Google Scholar
  74. Schipper, H., Brawer, J. R., Nelson, J. F., Felicio, L. S., and Finch, C. E., 1981, Role of the gonads in the histologic aging of the hypothalamic arcuate nucleus, Biol. Reprod. 25: 413–419.PubMedCrossRefGoogle Scholar
  75. Smith, P. E., 1963, Postponed pituitary homotransplants into the region of the hypophysial portal circulation in hypophysectomized female rats, Endocrinology 73: 793–806.PubMedCrossRefGoogle Scholar
  76. Steger, R. W., and Peluso, J. J., 1979, Hypothalamic-pituitary function in the older irregularly cycling rat, Exp. Aging Res. 5: 303–317.PubMedCrossRefGoogle Scholar
  77. Steger, R. W., Peluso, J. J., Huang, H. H., Hafez, E. S. E., and Meites, J., 1976, Gonadotrophin-binding sites in the ovary of aged rats, J. Reprod. Fertil. 48: 205–207.PubMedCrossRefGoogle Scholar
  78. Steger, R. W., Huang, H. H., and Meites, J., 1979a, Relation of aging to hypothalamic LHRH content and serum gonadal steroids in female rats, Proc. Soc. Exp. Biol. Med. 161: 251–254.PubMedGoogle Scholar
  79. Steger, R. W., Huang, H. H., and Meites, J., 1979b, Pulsatile LH release in old and young ovariectomized rats, Program of the 61st Annual Meeting of the Endocrine Society, Anaheim, California (Abst. 135 ), p. 106.Google Scholar
  80. Steger, R. W., Huang, H. H., Chamberlain, D. S., and Meites, J., 1980, Changes in control of gonadotropin secretion in the transition period between regular cycles and constant estrus in aging female rats, Biol. Reprod. 22: 595–603.PubMedCrossRefGoogle Scholar
  81. Van der Schoot, P., 1976, Changing pro-oestrous surges of luteinizing hormone in aging 5-day cyclic rats, J. Endocrinol. 69: 287–288.PubMedCrossRefGoogle Scholar
  82. Walker, R. F., 1981, Reproductive senescence and the dynamics of hypothalamic serotonin metabolism in the female rat, in: Brain Neurotransmitters and Receptors in Aging and Age-Related Disorders ( S. J. Enna, T. Samorajski, and B. Beer, eds.), Raven Press, New York, pp. 95–105.Google Scholar
  83. Watkins, B. E., McKay, D. W., Meites, J., and Riegle, G. D., 1975a, L-Dopa effects on serum LH and prolactin in old and young female rats, Neuroendocrinology 19: 331–338.PubMedCrossRefGoogle Scholar
  84. Watkins, B. E., Meites, J., and Riegle, G. D., 1975b, Age-related changes in pituitary responsiveness to LHRH in the female rat, Endocrinology 97: 543–548.PubMedCrossRefGoogle Scholar
  85. Wilkes, M. M., and Yen, S. S. C., 1981, Attenuation during aging in the postovariectomy rise in median eminence catecholamines, Neuroendocrinology 33: 144–147.PubMedCrossRefGoogle Scholar
  86. Wilkes, M. M., Lu, K. H., Hopper, B. R., and Yen, S. S. C., 1979, Altered neuroendocrine status of middle-aged rats prior to the onset of senescent anovulation, Neuroendocrinology 29: 255–261.PubMedCrossRefGoogle Scholar
  87. Wise, P. M., and Ratner, A., 1980, LHRH-induced LH and FSH responses in the aged female rat, J. Gerontol. 35: 506–511.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Pierre Aschheim
    • 1
  1. 1.Unité de Recherches GérontologiquesINSERM U.118ParisFrance

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