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

Koert de Vries, Csaba Nyakas, Brian P. den Hartog, Bauke Buwalda, Anton J.W. Scheurink, Roger A.H. Adan, Gertjan van Dijk

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Abstract

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
DOIs
Publication statusPublished - 2011

Keywords

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

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