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Brain melanocortin receptors are involved in CRH-mediated HPA axis activity and thermogenesis

de Vries, K., Nyakas, C., den Hartog, B. P., Buwalda, B., Scheurink, A. J. W., Adan, R. A. H. & van Dijk, G., 2011, In : The Open Neuroendocrinology Journal. 4, 1, p. 127-135 9 p.

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Recent studies indicate that corticotropin-releasing hormone (CRH) acts down-stream from brain melanocortin receptors (MC-Rs), however, much older evidence actually suggested the opposite. To reconcile this, rats were chronically infused centrally with the MC-R antagonist SHU9119 (0.5 nmol/day) over 14 days. Acute central CRH administration (0.5 μg) caused temporal anorexia, which was not impaired by SHU9119 treatment relative to controls. SHU9119 treatment, however, did attenuate CRH-induced plasma ACTH and thermogenic responses. Since SHU9119 pair-fed rats showed generally similar effects as SHU9119-treated ad libitum feeding rats, the modulation of ACTH and thermogenic responses are not secondary to increased body weight by SHU9119 treatment. Central pre-treatment with the glucocorticoid receptor agonist dexamethasone (10 μg) before CRH demonstrated that the inhibitory effect of SHU9119 treatment on the CRH-induced ACTH response was not attributed to increased glucocorticoid feedback. Peripheral dexamethasone pre-treatment (25 μg/kg rat), on the other hand, more potently suppressed CRH-induced corticosterone responses in SHU9119-treated rats. This effect is explained by sensitization of the adrenal cortex to glucocorticoid feedback as a result of SHU9119 treatment. We conclude that MC-Rs act down-stream from CRH to facilitate CRH-induced HPA axis activation and thermogenesis, but not down-stream from CRH to facilitate anorexia.
Original languageEnglish
Pages (from-to)127-135
Number of pages9
JournalThe Open Neuroendocrinology Journal
Volume4
Issue number1
Publication statusPublished - 2011

    Keywords

  • GR, CRH, HPA-axis, Central nervous system, Obesity, Melanocortins

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