Skip to main content
Log in

Administration of human leptin differentially affects parameters of cortisol secretion in socially housed female rhesus monkeys

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Chronic exposure to psychosocial stress may lead to a dysregulation of the limbic–hypothalamic–pituitary–adrenal axis that results in a number of adverse health outcomes. The fat-derived hormone leptin has been indicated as a potential key component to maintaining homeostasis by enhancing glucocorticoid negative feedback. Using an established model of nonhuman primate social stress, notably social subordination, this study examined the effects of continuous leptin administration on cortisol secretion in female rhesus monkeys. The 20 subjects were maintained in stable five-member social groups with established dominance hierarchies. All females were ovariectomized but received estradiol throughout the study to maintain serum concentrations at early follicular phase levels. Three parameters of cortisol secretion were examined in dominant and subordinate females during control and leptin-treatment conditions: diurnal cortisol secretion; response to a dexamethasone suppression test; and response to a brief separation from their social group. We hypothesized that leptin supplementation would attenuate the hypercortisolemia characteristic of subordinate females. During baseline conditions, subordinate female rhesus monkeys had significantly lower levels of serum leptin compared with more dominant monkeys and were less sensitive to glucocorticoid negative feedback. Exogenous administration of leptin improved glucocorticoid negative feedback in subordinate females and decreased morning cortisol in all animals. However, there were no status differences in response to a social separation test and diurnal rhythm in cortisol during baseline conditions. However, leptin administration did not attenuate the increase in cortisol in response to a social separation. The data presented in this study demonstrate that leptin can attenuate several parameters of cortisol secretion in female rhesus monkeys and thus may play a role in the response of the adrenal glands to socio-environmental stimuli.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. J.R. Kaplan, S.B. Manuck, T.B. Clarkson, F.M. Lusso, D.T. Taub, E.W. Miller, Science 220, 733 (1983)

    Article  CAS  PubMed  Google Scholar 

  2. A. Rozanski, J.A. Blumenthal, J.R. Kaplan, Circulation 99, 2192 (1999)

    CAS  PubMed  Google Scholar 

  3. T.L. Bale, Horm. Behav. 50, 529 (2006)

    Article  CAS  PubMed  Google Scholar 

  4. C.S. de Kloet, E. Vermetten, E. Geuze, A. Kavelaars, C.J. Heijnen, H.G. Westenberg, J. Psychiatr. Res. 40, 550 (2006)

    Article  PubMed  Google Scholar 

  5. S.A. French, M. Story, D. Neumark-Sztainer, B. Downes, M. Resnick, R. Blum, Int. J. Eat. Disord. 22, 315 (1997)

    Article  CAS  PubMed  Google Scholar 

  6. Y. Ueta, Y. Ozaki, J. Saito, T. Onaka, Exp. Biol. Med. 228, 1168 (2003)

    CAS  Google Scholar 

  7. S. Boullu-Ciocca, A. Dutour, V. Guillaume, V. Achard, C. Oliver, M. Grino, Diabetes 54, 197 (2005)

    Article  CAS  PubMed  Google Scholar 

  8. P. Bjorntorp, G. Holm, R. Rosmond, Diabet. Med. 16, 373 (1999)

    Article  CAS  PubMed  Google Scholar 

  9. G. Koob, M.J. Kreek, Am. J. Psychiatry 164, 1149 (2007)

    Article  PubMed  Google Scholar 

  10. S.L. Berga, T.L. Loucks, Minerva Ginecol. 57, 45 (2005)

    CAS  PubMed  Google Scholar 

  11. R.M. Sapolsky, Semin. Neurosci. 6, 261 (1994)

    Article  Google Scholar 

  12. G.E. Miller, A.K. Ritchey, S. Cohen, Health Psychol. 21, 531 (2002)

    Article  PubMed  Google Scholar 

  13. A.A. Zozulya, M.V. Gabaeva, O.Y. Sokolov, I.D. Surkina, N.V. Kost, J. Immunotoxicol. 5, 221 (2008)

    Article  PubMed  Google Scholar 

  14. D.B. Miller, J.P. O’Callaghan, Metab. Clin. Exp. 51, 5 (2002)

    CAS  PubMed  Google Scholar 

  15. S. Bhatnagar, M. Dallman, Neuroscience 84, 1025 (1998)

    Article  CAS  PubMed  Google Scholar 

  16. D.S. Albeck, C.R. McKittrick, D.C. Blanchard, R.J. Blanchard, J. Nikulina, B.S. McEwen, R.R. Sakai, J. Neurosci. 17, 4895 (1997)

    CAS  PubMed  Google Scholar 

  17. M.F. Dallman, N. Pecoraro, S.F. Akana, S.E. La Fleur, F. Gomez, H. Houshyar, M.E. Bell, S. Bhatnagar, K.D. Laugero, S. Manalo, Proc. Natl Acad. Sci. USA 100, 11696 (2003)

    Article  CAS  PubMed  Google Scholar 

  18. J.D. Shepard, K.W. Barron, D.A. Myers, Brain Res. 861, 288 (2000)

    Article  CAS  PubMed  Google Scholar 

  19. S.C. Stout, P. Mortas, M.J. Owens, C.B. Nemeroff, J. Moreau, Eur. J. Pharmacol. 401, 39 (2000)

    Article  CAS  PubMed  Google Scholar 

  20. M. Dallman, S. Bhatnagar, in Handbook of Physiology, Section 7: The Endocrine System, ed. by B. McEwen (Oxford University Press, New York, 2001)

    Google Scholar 

  21. G.N. Smagin, L.A. Howell, S. Redmann Jr., D.H. Ryan, R.B. Harris, Am. J. Physiol. 276, R1461 (1999)

    CAS  PubMed  Google Scholar 

  22. V.P. Bakshi, S.M. Newman, S. Smith-Roe, K.A. Jochman, N.H. Kalin, J. Neurosci. 27, 10568 (2007)

    Article  CAS  PubMed  Google Scholar 

  23. H.L. Fehm, W. Kern, A. Peters, Prog. Brain Res. 153, 129 (2006)

    Article  CAS  PubMed  Google Scholar 

  24. K.L. Tamashiro, M.M. Nguyen, T. Fujikawa, T. Xu, L. Yun Ma, S.C. Woods, R.R. Sakai, Physiol. Behav. 80, 683 (2004)

    Article  CAS  PubMed  Google Scholar 

  25. H. Jarrell, J.B. Hoffman, J.R. Kaplan, S. Berga, B. Kinkead, M.E. Wilson, Physiol. Behav. 93, 807 (2008)

    Article  CAS  PubMed  Google Scholar 

  26. L.K. Malendowicz, M. Rucinski, A.S. Belloni, A. Ziolkowska, G.G. Nussdorfer, Int. Rev. Cytol. 263, 63 (2007)

    Article  CAS  PubMed  Google Scholar 

  27. C.D. Walker, Prog. Neuropsychopharmacol. Biol. Psychiatry 29, 1249 (2005)

    Article  CAS  PubMed  Google Scholar 

  28. A. Giovambattista, A.N. Chisari, R.C. Gaillard, E. Spinedi, Neuroendocrinology 72, 341 (2000)

    Article  CAS  PubMed  Google Scholar 

  29. M.L. Heiman, R.S. Ahima, L.S. Craft, B. Schoner, T.W. Stephens, J.S. Flier, Endocrinology 138, 3859 (1997)

    Article  CAS  PubMed  Google Scholar 

  30. M. Oates, B. Woodside, C.D. Walker, Horm. Behav. 37, 366 (2000)

    Article  CAS  PubMed  Google Scholar 

  31. A. Kawakami, N. Okada, K. Rokkaku, K. Honda, S. Ishibashi, T. Onaka, Stress 11, 363 (2008)

    Article  CAS  PubMed  Google Scholar 

  32. K.W. Nowak, K. Pierzchala-Koziec, C. Tortorella, G.G. Nussdorfer, L.K. Malendowicz, Int. J. Mol. Med. 9, 61 (2002)

    CAS  PubMed  Google Scholar 

  33. M.E. Wilson, J. Fisher, J. Brown, Physiol. Behav. 84, 449 (2005)

    Article  CAS  PubMed  Google Scholar 

  34. T.L. Garthwaite, D.R. Martinson, L.F. Tseng, T.C. Hagen, L.A. Menahan, Endocrinology 107, 671 (1980)

    Article  CAS  PubMed  Google Scholar 

  35. Q. Huang, R. Rivest, D. Richard, Endocrinology 139, 1524 (1998)

    Article  CAS  PubMed  Google Scholar 

  36. K. Arvaniti, Q. Huang, D. Richard, Neuroendocrinology 73, 227 (2001)

    Article  CAS  PubMed  Google Scholar 

  37. K.L. Tamashiro, M.M. Nguyen, R.R. Sakai, Front. Neuroendocrinol. 26, 27 (2005)

    Article  PubMed  Google Scholar 

  38. I.S. Bernstein, J. Theor. Biol. 60, 459 (1976)

    Article  CAS  PubMed  Google Scholar 

  39. I.S. Bernstein, T.P. Gordon, Am. Sci. 62, 304 (1974)

    CAS  PubMed  Google Scholar 

  40. I.S. Bernstein, T.P. Gordon, R.M. Rose, Folia Primatol. 21, 81 (1974)

    Article  CAS  PubMed  Google Scholar 

  41. C. Shively, J. Kaplan, Physiol. Behav. 33, 777 (1984)

    Article  CAS  PubMed  Google Scholar 

  42. D.H. Abbott, E.B. Keverne, F.B. Bercovitch, C.A. Shively, S.P. Mendoza, W. Saltzman, C.T. Snowdon, T.E. Ziegler, M. Banjevic, T. Garland, R.M. Sapolsky, Horm. Behav. 43, 67 (2003)

    Article  CAS  PubMed  Google Scholar 

  43. J.R. Kaplan, M.R. Adams, T.B. Clarkson, D.R. Koritnik, Atherosclerosis 53, 283 (1984)

    Article  CAS  PubMed  Google Scholar 

  44. S. Cohen, Ann. N. Y. Acad. Sci. 896, 246 (1999)

    Article  CAS  PubMed  Google Scholar 

  45. M.E. Wilson, J. Fisher, A. Fischer, V. Lee, R.B. Harris, T.J. Bartness, Physiol. Behav. 94, 586 (2008)

    Article  CAS  PubMed  Google Scholar 

  46. M.E. Wilson, K. Pazol, A. Legendre, J. Fisher, K. Chikazawa, Endocrine 26, 89 (2006)

    Article  Google Scholar 

  47. M. Paiardini, J. Hoffman, B. Cervasi, A.M. Ortiz, F. Stroud, G. Silvestri, M.E. Wilson, Brain Behav. Immun. 23, 286 (2009)

    Article  CAS  PubMed  Google Scholar 

  48. C.A. Shively, K. Laber-Laird, R.F. Anton, Biol. Psychiatry 41, 871 (1997)

    Article  CAS  PubMed  Google Scholar 

  49. C.A. Shively, Biol. Psychiatry 44, 882 (1998)

    Article  CAS  PubMed  Google Scholar 

  50. J.R. Kaplan, M.R. Adams, T.B. Clarkson, S.B. Manuck, C.A. Shively, J.K. Williams, Psychosom. Med. 58, 598 (1996)

    CAS  PubMed  Google Scholar 

  51. D. Morgan, K.A. Grant, H.D. Gage, R.H. Mach, J.R. Kaplan, O. Prioleau, S.H. Nader, N. Buchheimer, R.L. Ehrenkaufer, M.A. Nader, Nat. Neurosci. 5, 169 (2002)

    Article  CAS  PubMed  Google Scholar 

  52. K.A. Grant, C.A. Shively, M.A. Nader, R.L. Ehrenkaufer, S.W. Line, T.E. Morton, H.D. Gage, R.H. Mach, Synapse 29, 80 (1998)

    Article  CAS  PubMed  Google Scholar 

  53. C.A. Shively, D.P. Friedman, H.D. Gage, M.C. Bounds, C. Brown-Proctor, J.B. Blair, J.A. Henderson, M.A. Smith, N. Buchheimer, Arch. Gen. Psychiatry 63, 396 (2006)

    Article  CAS  PubMed  Google Scholar 

  54. J.R. Kaplan, S.B. Manuck, ILAR 45, 89 (2004)

    CAS  Google Scholar 

  55. D.A. Gust, T.P. Gordon, M.E. Wilson, A. Ahmed-Ansari, A.R. Brodie, H.M. McClure, Brain Behav. Immun. 5, 296 (1991)

    Article  CAS  PubMed  Google Scholar 

  56. C.A. Shively, T.C. Register, D.P. Friedman, T.M. Morgan, J. Thompson, T. Lanier, Biol. Psychol. 69, 67 (2005)

    Article  PubMed  Google Scholar 

  57. A. Troisi, Stress 5, 47 (2002)

    Article  PubMed  Google Scholar 

  58. C.A. Czeisler, E.B. Klerman, Recent Prog. Horm. Res. 54, 97 (1999)

    CAS  PubMed  Google Scholar 

  59. R.E. Dahl, Semin. Pediatr. Neurol. 3, 44 (1996)

    Article  CAS  PubMed  Google Scholar 

  60. A. Sadeh, R. Gruber, A. Raviv, Child Dev. 73, 405 (2002)

    Article  PubMed  Google Scholar 

  61. A. Oskis, C. Loveday, F. Hucklebridge, L. Thorn, A. Clow, Psychoneuroendocrinology 34, 307 (2009)

    Article  CAS  PubMed  Google Scholar 

  62. S. Bhatnagar, C. Vining, Horm. Behav. 43, 158 (2003)

    Article  CAS  PubMed  Google Scholar 

  63. C.M. Berman, K.L. Rasmussen, S.J. Suomi, Child Dev. 65, 1028 (1994)

    Article  CAS  PubMed  Google Scholar 

  64. D.A. Gust, T.P. Gordon, M.K. Hambright, Physiol. Behav. 53, 599 (1993)

    Article  CAS  PubMed  Google Scholar 

  65. S.R. Bornstein, K. Uhlmann, A. Haidan, M. Ehrhart-Bornstein, W.A. Scherbaum, Diabetes 46, 1235 (1997)

    Article  CAS  PubMed  Google Scholar 

  66. F.P. Pralong, R. Roduit, G. Waeber, E. Castillo, F. Mosimann, B. Thorens, R.C. Gaillard, Endocrinology 139, 4264 (1998)

    Article  CAS  PubMed  Google Scholar 

  67. H.T. Hsu, Y.C. Chang, Y.N. Chiu, C.L. Liu, K.J. Chang, I.C. Guo, J. Clin. Endocrinol. Metab. 91, 2761 (2006)

    Article  CAS  PubMed  Google Scholar 

  68. M. Sone, R.Y. Osamura, Pituitary 4, 15 (2001)

    Article  CAS  PubMed  Google Scholar 

  69. J. Harvey, J. Neurochem. 100, 307 (2007)

    Article  CAS  PubMed  Google Scholar 

  70. S. Diano, S.P. Kalra, H. Sakamoto, T.L. Horvath, Brain Res. 812, 256 (1998)

    Article  CAS  PubMed  Google Scholar 

  71. P.D. Finn, M.J. Cunningham, D.G. Rickard, D.K. Clifton, R.A. Steiner, J. Clin. Endocrinol. Metab. 86, 422 (2001)

    Article  CAS  PubMed  Google Scholar 

  72. S. Fulton, P. Pissios, R.P. Manchon, L. Stiles, L. Frank, E.N. Pothos, E. Maratos-Flier, J.S. Flier, Neuron 51, 811 (2006)

    Article  CAS  PubMed  Google Scholar 

  73. J.G. Mercer, K.M. Moar, N. Hoggard, Endocrinology 139, 29 (1998)

    Article  CAS  PubMed  Google Scholar 

  74. J.T. Smith, B.V. Acohido, D.K. Clifton, R.A. Steiner, J. Neuroendocrinol. 18, 298 (2006)

    Article  CAS  PubMed  Google Scholar 

  75. J. Harvey, N. Solovyova, A. Irving, Prog. Lipid Res. 45, 369 (2006)

    Article  CAS  PubMed  Google Scholar 

  76. X.Y. Lu, C.S. Kim, A. Frazer, W. Zhang, Proc. Natl Acad. Sci. USA 103, 1593 (2006)

    Article  CAS  PubMed  Google Scholar 

  77. J.D. Gardner, N.J. Rothwell, G.N. Luheshi, Nat. Neurosci. 1, 103 (1998)

    Article  CAS  PubMed  Google Scholar 

  78. M. Nikodemova, C.R. Diehl, G. Aguilera, Arch. Physiol. Biochem. 110, 123 (2002)

    Article  CAS  PubMed  Google Scholar 

  79. K.J. Kovacs, A. Fioldes, P.E. Sawchenko, J. Neurosci. 20, 3843 (2000)

    CAS  PubMed  Google Scholar 

  80. J.P. Herman, D. Adams, C. Prewitt, Neuroendocrinology 61, 180 (1995)

    Article  CAS  PubMed  Google Scholar 

  81. K. Proulx, S. Clavel, G. Nault, D. Richard, C.D. Walker, Endocrinology 142, 4607 (2001)

    Article  CAS  PubMed  Google Scholar 

  82. M.P. Howell, L.J. Muglia, Front. Neuroendocrinol. 27, 275 (2006)

    Article  CAS  PubMed  Google Scholar 

  83. M.P. Warren, F. Voussoughian, E.B. Geer, E.P. Hyle, C.L. Adberg, R.H. Ramos, J. Clin. Endocrinol. Metab. 84, 873 (1999)

    Article  CAS  PubMed  Google Scholar 

  84. A.J. Tilbrook, E.A. Rivalland, A.I. Turner, G.W. Lambert, I.J. Clarke, Neuroendocrinology 87, 193 (2008)

    Article  CAS  PubMed  Google Scholar 

  85. M.E. Gluck, A. Geliebter, M. Lorence, Ann. N. Y. Acad. Sci. 1032, 202 (2004)

    Article  CAS  PubMed  Google Scholar 

  86. C.D. Morrison, Physiol. Behav. 94, 660 (2008)

    Article  CAS  PubMed  Google Scholar 

  87. O. Johren, A. Dendorfer, P. Dominiak, W. Raasch, Brain Res. 1184, 160 (2007)

    Article  PubMed  CAS  Google Scholar 

  88. M.F. Dallman, N.C. Pecoraro, S.E. La Fleur, Brain Behav. Immun. 19, 275 (2005)

    Article  PubMed  Google Scholar 

  89. K.L. Tamashiro, M.A. Hegeman, R.R. Sakai, Physiol. Behav. 89, 536 (2006)

    Article  CAS  PubMed  Google Scholar 

  90. S.E. La Fleur, H. Houshyar, M. Roy, M.F. Dallman, Endocrinology 146, 2193 (2005)

    Article  CAS  PubMed  Google Scholar 

  91. N. Pecoraro, F. Reyes, F. Gomez, A. Bhargava, M.F. Dallman, Endocrinology 145, 3754 (2004)

    Article  CAS  PubMed  Google Scholar 

  92. M.T. Foster, J.P. Warne, A.B. Ginsberg, H.F. Horneman, N.C. Pecoraro, S.F. Akana, M.F. Dallman, Endocrinology 150, 2325 (2009)

    Article  CAS  PubMed  Google Scholar 

  93. J.B. Hoffman, J.R. Kaplan, B. Kinkead, S.L. Berga, M.E. Wilson, Endocrine 31, 202 (2007)

    Article  CAS  PubMed  Google Scholar 

  94. M.E. Wilson, T.P. Gordon, J.M. Tanner, J. Endocrinol. 137, 519 (1993)

    Article  CAS  PubMed  Google Scholar 

  95. M.L. Barker-Gibb, A. Sahu, C.R. Pohl, T.M. Plant, J. Clin. Endocrinol. Metab. 87, 4976 (2002)

    Article  CAS  PubMed  Google Scholar 

  96. M.E. Wilson, J. Fisher, K. Chikazawa, R. Yoda, A. Legendre, D. Mook, K.G. Gould, J. Clin. Endocrinol. Metab. 88, 4874 (2003)

    Article  CAS  PubMed  Google Scholar 

  97. M.E. Wilson, A. Legendre, K. Pazol, J. Fisher, K. Chikazawa, Endocrine 26, 89 (2005)

    Article  CAS  PubMed  Google Scholar 

  98. S.M. Brooke, A.M. de Haas-Johnson, J.R. Kaplan, S.B. Manuck, R.M. Sapolsky, Neuroendocrinology 60, 134 (1994)

    Article  CAS  PubMed  Google Scholar 

  99. C.A. Shively, J.K. Williams, K. Laber-Laird, R.F. Anton, Psychosom. Med. 64, 699 (2002)

    Article  PubMed  Google Scholar 

  100. M.S. Blank, T.P. Gordon, M.E. Wilson, Acta Endocrinol. 102, 190 (1983)

    CAS  PubMed  Google Scholar 

  101. M.L. Walker, T.P. Gordon, M.E. Wilson, J. Med. Primatol. 11, 291 (1982)

    CAS  PubMed  Google Scholar 

  102. M.L. Walker, M.E. Wilson, T.P. Gordon, Endocrinology 114, 1074 (1984)

    Article  CAS  PubMed  Google Scholar 

  103. K. Wallen, P.L. Tannenbaum, Ann. N. Y. Acad. Sci. 807, 185 (1997)

    Article  CAS  PubMed  Google Scholar 

  104. K. Pazol, J.R. Kaplan, D. Abbott, S.E. Appt, M.E. Wilson, Clin. Chim. Acta 340, 117 (2004)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The technical assistance of Jeffrey Fisher, Jennifer Whitley, and Holly Jarrell is greatly appreciated. This study was funded by NIH grants HD46501, training Grants nos. 4425 RR024505 (for LAC) and K12 GM000680 for (JBH), and, in part, RR00165. The YNPRC is fully accredited by AAALAC, International.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mark E. Wilson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Collura, L.A., Hoffman, J.B. & Wilson, M.E. Administration of human leptin differentially affects parameters of cortisol secretion in socially housed female rhesus monkeys. Endocr 36, 530–537 (2009). https://doi.org/10.1007/s12020-009-9250-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-009-9250-7

Keywords

Navigation