Abstract
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.
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Nemeroff, C. B., Grant, L. D., Bissette, G., Erin, G. N., Harrell, L. E., and Prange, A. J. (1977). Psychoneuroendocrinology 2, 179–196.
Holzwarth-McBride, M. A., Sladek, J. R. Jr., and Knigge, K. M. (1976). Anat. Rec. 186, 197–205.
Krieger, D. T., Liotta, A. S., Nicholsen, G., and Kizer, J. S. (1979). Nature 278, 562–563.
Olney, J. W. and Sharpe, L. G. (1969). Science 166, 386–388.
Burde, R. M., Schainker, B., and Kayes, J. (1971). Nature 233, 58–60.
Redding, T. W., Schally, A. V., Arimura, A., and Wakabayashi, I. (1971). Neuroendocrinology 8, 245–255.
Larsen, P. J., Mikkelsen, J. D., Jessop, D., Lightman, S. L., and Chowdrey, H. S. (1994). J. Endocrinol. 141, 497–503.
Skultetyova, I., Kiss, A., and Jezova, D. (1998). Neuroendocrinology 67, 412–420.
Macho, L., Jezova, D., Zorad, S., and Fickova, M. (1999). Endocr. Regul. 33, 61–67.
Dolnikoff, M. S., Kater, C. E., Egami, M., de Andrade, I. S., and Marmo, M. R. (1988). Neuroendocrinology 48, 645–649.
Morris, M. J., Tortelli, C. F., Filippis, A., and Proietto, J. (1998). Regul. Pept. 75–76, 441–447.
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.
DePaolo, L. V. and Negro-Vilar, A. (1982). Endocrinology 110, 835–841.
Spinedi, E., Johnston, C. A., and Negro-Vilar, A. (1984). Endocrinology 115, 267–272.
Badger, T. M., Millard, W. J., Martin, J. B., Rosenblum, P. M., and Levenson, S. E. (1982). Endocrinology 111, 2031–2038.
Bliss, E. L., Ailion, J., and Zwanziger, J. (1968). J. Pharmacol. Exp. Ther. 164, 122–134.
Palkovits, M., Brownstein, M., Kizer, J. S., Saavedra, J. M., and Kopin, I. J. (1976). Neuroendocrinology 22, 298–304.
Dawson, R., Pelleymounter, M. A., Millard, W. J., Liu, S., and Eppler, B. (1997). Am. J. Physiol. 273, E202-E206.
Spinedi, E. and Gaillard, R. C. (1998). Endocrinology 139, 4016–4020.
Hamann, A. and Matthaei, S. (1996). Exp. Clin. Endocrinol. Diabetes 104, 293–300.
Pralong, F. P., Roduit, R., Waeber, G., et al. (1998). Endocrinology 139, 4264–4268.
Kaneko, M., Hiroshige, T., Shinsako, J., and Dallman, M. F. (1980). Am. J. Physiol. 239, R309-R316.
Olney, J. W. (1969). Science 164, 719–721.
Cowley, M. A., Smart, J. L., Rubinstein, M., et al. (2001). Nature 411, 480–484.
Kalra, S. P., Dube, M. G., Pu, S., Xu, B., Horvath, T. L., and Kalra, P. S. (1999). Endocr. Rev. 20, 68–100.
Holsboer, F. and Barden, N. (1996). Endocr. Rev. 17, 187–205.
Heiman, M. L., Ahima, R. S., Craft, L. S., Schoner, B., Stephens, T. W., and Flier, J. S. (1997). Endocrinology 138, 3859–3863.
Giovambattista, A., Chisari, A. N., Gaillard, R. C., and Spinedi, E. (2000). Neuroendocrinology 72, 341–349.
Tena-Sempere, M., Pinilla, L., Gonzalez, L. C., Casanueva, F. F., Dieguez, C., and Aguilar, E. (2000). J. Endocrinol. 167, 479–486.
Sahu, A. (2003). Front. Neuroendocrinol. 24, 225–253.
Sahu, A. (2004). Endocrinology 144, 3789–3798.
Perello, A., Gaillard, R.C., Chisari, A. N., and Spinedi, E. (2003). Neuroendocrinology 78, 176–184.
Daneva, T., Spinedi, E., Hadid, R., and Gaillard, R. C. (1995). Neuroendocrinology 62, 79–86.
Spinedi, E., Aguado, L., Basilotta, G., and Carrizo, D. (1989). J. Endocrinol. Invest. 12, 321–327.
Cónsole, G. M., Jurado, S. B., Petruccelli. M., Carino, M., Calandra, R. S., and Gómez Dumm, C. L. A. (2002). Neuroendocrinology 75, 316–325.
Spinedi, E., Giacomini, M., Jacquier, M. C., and Gaillard, R. C. (1991). Neuroendocrinology 53, 160–170.
Chomczynski, P. and Sacchi, N. (1987). Anal. Biochem. 162, 156–159.
Giovambattista, A., Chisari, A. N., Corro, L., Gaillard, R. C., and Spinedi, E. (2000). Neuroimmunomodulation 7, 92–98.
Spinedi, E. and Negro-Vilar, A. (1984). Endocrinology 114, 2247–2251.
McElroy, W. D., and Swanson, C. P. (eds.) (1974). Biostatistical analysis. Prentice-Hall: Englewood Cliffs, N.J.
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Perelló, M., Moreno, G., Camihort, G. et al. Nature of changes in adrenocortical function in chronic hyperleptinemic female rats. Endocr 24, 167–175 (2004). https://doi.org/10.1385/ENDO:24:2:167
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DOI: https://doi.org/10.1385/ENDO:24:2:167