, Volume 24, Issue 2, pp 167–175 | Cite as

Nature of changes in adrenocortical function in chronic hyperleptinemic female rats

  • Mario Perelló
  • Griselda Moreno
  • Gisela Camihort
  • Georgina Luna
  • Gloria Cónsole
  • Rolf C. Gaillard
  • Eduardo Spinedi
Original Articles


Neonatal treatment of rats with monosodium l-glutamate, which destroys hypothalamic arcuate nucleus neuronal bodies, induces several metabolic abnormalities; as a result, rats develop a phenotype of pseudoobesity. This study was designed to explore, in the monosodium l-glutamate-treated female rat, the influence of chronic hyperleptinemia on adrenal cortex functionality. For this purpose, we evaluated in control and hypothalamic-damaged rats: (a) in vivo and in vitro adrenocortical function, (b) adrenal leptin receptor immunodistribution and mRNA expression, and (c) whether the inhibitory effect of leptin on adrenal function remains. Our results indicate that, compared to normal counterparts, pseudoobese animals displayed (1) hyperadiposity, despite being hypophagic and of lower body weight, (2) in vivo and in vitro enhanced adrenocortical response to ACTH stimulation, (3) an in vitro adrenal fasciculata-reticularis cell hyper-sensitivity to ACTH stimulus, (4) hyperplasia of their adrenal zona fasciculata cells, and (5) adrenal fasciculata-reticularis cell refractoriness to the inhibitory effect of leptin on ACTH-stimulated glucocorticoid production due, at least in part, to decreased adrenal leptin receptor expression. These data further support that increased hypothalamo-pituitary-adrenal axis function, in the adult neurotoxin-lesioned female rat, is mainly dependent on the development of both hyperplasia of adrenal zona fasciculata and adrenal gland refractoriness to leptin inhibitory effect. Our study supports that adrenal leptin resistance could be responsible, at least in part, for enhanced glucocorticoid circulating levels in this phenotype of obesity.

Key Words

ARC damage hypothalamic obesity positive energetic balance Ob-Rb adiposity adrenal gland glucocorticoid leptin 


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  1. 1.
    Nemeroff, C. B., Grant, L. D., Bissette, G., Erin, G. N., Harrell, L. E., and Prange, A. J. (1977). Psychoneuroendocrinology 2, 179–196.PubMedCrossRefGoogle Scholar
  2. 2.
    Holzwarth-McBride, M. A., Sladek, J. R. Jr., and Knigge, K. M. (1976). Anat. Rec. 186, 197–205.PubMedCrossRefGoogle Scholar
  3. 3.
    Krieger, D. T., Liotta, A. S., Nicholsen, G., and Kizer, J. S. (1979). Nature 278, 562–563.PubMedCrossRefGoogle Scholar
  4. 4.
    Olney, J. W. and Sharpe, L. G. (1969). Science 166, 386–388.PubMedCrossRefGoogle Scholar
  5. 5.
    Burde, R. M., Schainker, B., and Kayes, J. (1971). Nature 233, 58–60.PubMedCrossRefGoogle Scholar
  6. 6.
    Redding, T. W., Schally, A. V., Arimura, A., and Wakabayashi, I. (1971). Neuroendocrinology 8, 245–255.PubMedGoogle Scholar
  7. 7.
    Larsen, P. J., Mikkelsen, J. D., Jessop, D., Lightman, S. L., and Chowdrey, H. S. (1994). J. Endocrinol. 141, 497–503.PubMedCrossRefGoogle Scholar
  8. 8.
    Skultetyova, I., Kiss, A., and Jezova, D. (1998). Neuroendocrinology 67, 412–420.PubMedCrossRefGoogle Scholar
  9. 9.
    Macho, L., Jezova, D., Zorad, S., and Fickova, M. (1999). Endocr. Regul. 33, 61–67.PubMedGoogle Scholar
  10. 10.
    Dolnikoff, M. S., Kater, C. E., Egami, M., de Andrade, I. S., and Marmo, M. R. (1988). Neuroendocrinology 48, 645–649.PubMedGoogle Scholar
  11. 11.
    Morris, M. J., Tortelli, C. F., Filippis, A., and Proietto, J. (1998). Regul. Pept. 75–76, 441–447.PubMedCrossRefGoogle Scholar
  12. 12.
    Miller, R. J. and Dawson, G. (1979). In: Receptor for neurotransmitters and peptide hormones. Pepeu, G., Kuhar, M. J., and Enna, S. J. (eds.). Raven Press: New York.Google Scholar
  13. 13.
    DePaolo, L. V. and Negro-Vilar, A. (1982). Endocrinology 110, 835–841.PubMedGoogle Scholar
  14. 14.
    Spinedi, E., Johnston, C. A., and Negro-Vilar, A. (1984). Endocrinology 115, 267–272.PubMedCrossRefGoogle Scholar
  15. 15.
    Badger, T. M., Millard, W. J., Martin, J. B., Rosenblum, P. M., and Levenson, S. E. (1982). Endocrinology 111, 2031–2038.PubMedGoogle Scholar
  16. 16.
    Bliss, E. L., Ailion, J., and Zwanziger, J. (1968). J. Pharmacol. Exp. Ther. 164, 122–134.PubMedGoogle Scholar
  17. 17.
    Palkovits, M., Brownstein, M., Kizer, J. S., Saavedra, J. M., and Kopin, I. J. (1976). Neuroendocrinology 22, 298–304.PubMedGoogle Scholar
  18. 18.
    Dawson, R., Pelleymounter, M. A., Millard, W. J., Liu, S., and Eppler, B. (1997). Am. J. Physiol. 273, E202-E206.PubMedGoogle Scholar
  19. 19.
    Spinedi, E. and Gaillard, R. C. (1998). Endocrinology 139, 4016–4020.PubMedCrossRefGoogle Scholar
  20. 20.
    Hamann, A. and Matthaei, S. (1996). Exp. Clin. Endocrinol. Diabetes 104, 293–300.PubMedCrossRefGoogle Scholar
  21. 21.
    Pralong, F. P., Roduit, R., Waeber, G., et al. (1998). Endocrinology 139, 4264–4268.PubMedCrossRefGoogle Scholar
  22. 22.
    Kaneko, M., Hiroshige, T., Shinsako, J., and Dallman, M. F. (1980). Am. J. Physiol. 239, R309-R316.PubMedGoogle Scholar
  23. 23.
    Olney, J. W. (1969). Science 164, 719–721.PubMedCrossRefGoogle Scholar
  24. 24.
    Cowley, M. A., Smart, J. L., Rubinstein, M., et al. (2001). Nature 411, 480–484.PubMedCrossRefGoogle Scholar
  25. 25.
    Kalra, S. P., Dube, M. G., Pu, S., Xu, B., Horvath, T. L., and Kalra, P. S. (1999). Endocr. Rev. 20, 68–100.PubMedCrossRefGoogle Scholar
  26. 26.
    Holsboer, F. and Barden, N. (1996). Endocr. Rev. 17, 187–205.PubMedCrossRefGoogle Scholar
  27. 27.
    Heiman, M. L., Ahima, R. S., Craft, L. S., Schoner, B., Stephens, T. W., and Flier, J. S. (1997). Endocrinology 138, 3859–3863.PubMedCrossRefGoogle Scholar
  28. 28.
    Giovambattista, A., Chisari, A. N., Gaillard, R. C., and Spinedi, E. (2000). Neuroendocrinology 72, 341–349.PubMedCrossRefGoogle Scholar
  29. 29.
    Tena-Sempere, M., Pinilla, L., Gonzalez, L. C., Casanueva, F. F., Dieguez, C., and Aguilar, E. (2000). J. Endocrinol. 167, 479–486.PubMedCrossRefGoogle Scholar
  30. 30.
    Sahu, A. (2003). Front. Neuroendocrinol. 24, 225–253.PubMedCrossRefGoogle Scholar
  31. 31.
    Sahu, A. (2004). Endocrinology 144, 3789–3798.Google Scholar
  32. 32.
    Perello, A., Gaillard, R.C., Chisari, A. N., and Spinedi, E. (2003). Neuroendocrinology 78, 176–184.PubMedCrossRefGoogle Scholar
  33. 33.
    Daneva, T., Spinedi, E., Hadid, R., and Gaillard, R. C. (1995). Neuroendocrinology 62, 79–86.PubMedGoogle Scholar
  34. 34.
    Spinedi, E., Aguado, L., Basilotta, G., and Carrizo, D. (1989). J. Endocrinol. Invest. 12, 321–327.PubMedGoogle Scholar
  35. 35.
    Cónsole, G. M., Jurado, S. B., Petruccelli. M., Carino, M., Calandra, R. S., and Gómez Dumm, C. L. A. (2002). Neuroendocrinology 75, 316–325.PubMedCrossRefGoogle Scholar
  36. 36.
    Spinedi, E., Giacomini, M., Jacquier, M. C., and Gaillard, R. C. (1991). Neuroendocrinology 53, 160–170.PubMedGoogle Scholar
  37. 37.
    Chomczynski, P. and Sacchi, N. (1987). Anal. Biochem. 162, 156–159.PubMedCrossRefGoogle Scholar
  38. 38.
    Giovambattista, A., Chisari, A. N., Corro, L., Gaillard, R. C., and Spinedi, E. (2000). Neuroimmunomodulation 7, 92–98.PubMedCrossRefGoogle Scholar
  39. 39.
    Spinedi, E. and Negro-Vilar, A. (1984). Endocrinology 114, 2247–2251.PubMedCrossRefGoogle Scholar
  40. 40.
    McElroy, W. D., and Swanson, C. P. (eds.) (1974). Biostatistical analysis. Prentice-Hall: Englewood Cliffs, N.J.Google Scholar

Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  • Mario Perelló
    • 1
  • Griselda Moreno
    • 1
  • Gisela Camihort
    • 2
  • Georgina Luna
    • 2
  • Gloria Cónsole
    • 2
  • Rolf C. Gaillard
    • 3
  • Eduardo Spinedi
    • 1
  1. 1.Neuroendocrine UnitMultidisciplinary Institute on Cell Biology (CONICET-CICPBA)La PlataArgentina
  2. 2.Department of Histology and Embryology “B,” School of MedicineUNLP-CICPBALa PlataArgentina
  3. 3.Division of Endocrinology, Diabetology & MetabolismUniversity Hospital (CHUV)LausanneSwitzerland

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