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Peer-reviewed veterinary case report

Melanocortin 2 receptor blockers reduce cortisol in dog adrenal cells

By Sanders, Karin et al.·Published in Veterinary research communications·2018·Department of Clinical Sciences of Companion Animals, Netherlands·View original on PubMed

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Original publication title: Melanocortin 2 receptor antagonists in canine pituitary-dependent hypercortisolism: in vitro studies.

Species:
dog

Plain-English summary

A study looked at two new compounds that might help treat dogs with pituitary-dependent hypercortisolism, a condition where the body produces too much cortisol. In tests with dog adrenal cells, one compound (#299) was found to significantly reduce cortisol production when stimulated by a hormone called ACTH. This suggests that #299 could be a promising treatment option for dogs suffering from this condition, but more research is needed to see how well it works in actual dogs.

People also search for: dog hypercortisolism treatment · pituitary gland problems in dogs · cortisol levels in dogs

Abstract

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.

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Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/30187173/