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Orexin a stimulates hypothalamic-pituitary-adrenal (HPA) axis function, but not food intake, in the absence of full hypothalamic NPY-ergic activity

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Abstract

Neonatal monosodium l-glutamate (MSG) treatment destroys hypothalamic arcuate nucleus neuronal bodies, thus inducing several metabolic abnormalities. As a result, rats develop a phenotype characterized by hyperleptinemia and by impaired NPY but normal prepro-orexin hypothalamic mRNAs expression. Thus, our study was designed to explore whether hypothalamic effects of orexin A on food intake and glucocorticoid production develop in the absence of full hypothalamic NPY-ergic activity. For this purpose we evaluated, in control and MSG-treated rats, the consequences of intracere-broventricular (icv) orexin A administration on food intake and changes in circulating levels of ACTH and glucocorticoid. Our results indicate that orexin A icv treatment stimulated hypothalamic-pituitary-adrenal (HPA) axis activity in both MSG-damaged and normal animals, with this response even more pronounced in neurotoxin-damaged rats. Conversely, food intake was only enhanced by icv orexin A injection in normal rats. Our study further supports that acute hypothalamic effects of orexin A on food intake and glucocorticoid production are due to independent neuronal systems. While intact arcuate nucleus activity is needed for the orexinergic effect induced by icv orexin A administration, conversely, orexin A-stimulated HPA axis function takes place even in the absence of full NPY-ergic activity.

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Authors and Affiliations

  1. Neuroendocrine Unit, Multidisciplinary Institute on Cell Biology (CONICET-CICPBA), 1900, La Plata, Argentina

    Griselda Moreno, Mario Perelló &  Eduardo Spinedi

  2. Division of Endocrinology, Diabetology and Metabolism, University Hospital (CHUV), CH 1011, Lausanne, Switzerland

    Rolf C. Gaillard

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  1. Griselda Moreno
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  2. Mario Perelló
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  3. Rolf C. Gaillard
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  4. Eduardo Spinedi
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Correspondence to Eduardo Spinedi.

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Moreno, G., Perelló, M., Gaillard, R.C. et al. Orexin a stimulates hypothalamic-pituitary-adrenal (HPA) axis function, but not food intake, in the absence of full hypothalamic NPY-ergic activity. Endocr 26, 99–106 (2005). https://doi.org/10.1385/ENDO:26:2:099

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  • DOI: https://doi.org/10.1385/ENDO:26:2:099

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