Melanocortin 2 receptor antagonists in canine pituitary-dependent hypercortisolism: in vitro studies: in vitro studies

Karin Sanders, Jan A. Mol, Hans S. Kooistra, Sara Galac

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

9 Citaten (Scopus)


Canine hypercortisolism is most often caused by an ACTH-secreting pituitary adenoma (pituitary-dependent hypercortisolism; PDH). An interesting target for a selective medical treatment of PDH would be the receptor for ACTH: the melanocortin 2 receptor (MC2R). In this study we investigated whether two peptide compounds, BIM-22776 (#776) and BIM-22A299 (#299), are effective MC2R antagonists in vitro. Their effects on cortisol production and mRNA expression of steroidogenic enzymes, MC2R and melanocortin 2 receptor accessory protein (MRAP) were evaluated in primary adrenocortical cell cultures (n = 8) of normal canine adrenal glands. Cortisol production stimulated by 50 nM ACTH was dose-dependently inhibited by #299 (inhibition 90.7 ± 2.3% at 5 μM) and by #776 (inhibition 38.0 ± 5.2% at 5 μM). The ACTH-stimulated mRNA expression of steroidogenic enzymes, MC2R and MRAP was significantly inhibited by both compounds, but most potently by #299. These results indicate that canine primary cell culture is a valuable in vitro system to test MC2R antagonists, and that these compounds, but especially #299, are effective MC2R antagonists in vitro. To determine its efficacy in vivo, further studies are warranted. Antagonism of the MC2R is a promising potential treatment approach in canine PDH.
Originele taal-2Nederlands
Pagina's (van-tot)283-288
Aantal pagina's6
TijdschriftVeterinary Research Communications
Nummer van het tijdschrift4
StatusGepubliceerd - 1 dec. 2018
Extern gepubliceerdJa


  • ACTH
  • Cushing’s syndrome
  • Dog
  • MC2R
  • PDH
  • Treatment

Citeer dit