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

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

Research output: Contribution to journalArticle

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
JournalOpen Neuroendocrinology Journal
Volume4
DOIs
Publication statusPublished - 2011

Fingerprint

Melanocortin Receptors
Thermogenesis
Corticotropin-Releasing Hormone
Brain
Adrenocorticotropic Hormone
Anorexia
Dexamethasone
Glucocorticoids
SHU 9119
Adrenal Cortex
Glucocorticoid Receptors
Corticosterone
Body Weight

Keywords

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

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Endocrinology, Diabetes and Metabolism

Cite this

de Vries, K., Nyakas, C., den Hartog, B. P., Buwalda, B., Scheurink, A. J. W., Adan, R. A. H., & van Dijk, G. (2011). Brain melanocortin receptors are involved in CRH-mediated HPA axis activity and thermogenesis. Open Neuroendocrinology Journal, 4, 127-135. https://doi.org/10.2174/1876528901104010127

Brain melanocortin receptors are involved in CRH-mediated HPA axis activity and thermogenesis. / de Vries, Koert; Nyakas, C.; den Hartog, Brian P.; Buwalda, Bauke; Scheurink, Anton J W; Adan, Roger A H; van Dijk, Gertjan.

In: Open Neuroendocrinology Journal, Vol. 4, 2011, p. 127-135.

Research output: Contribution to journalArticle

de Vries, Koert ; Nyakas, C. ; den Hartog, Brian P. ; Buwalda, Bauke ; Scheurink, Anton J W ; Adan, Roger A H ; van Dijk, Gertjan. / Brain melanocortin receptors are involved in CRH-mediated HPA axis activity and thermogenesis. In: Open Neuroendocrinology Journal. 2011 ; Vol. 4. pp. 127-135.
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