Abstract
BackgroundGlucocorticoids, among the most widely utilized drugs in veterinary medicine, are employed to treat a wide variety of diseases; however, their use often induces adverse events in dogs. The efficacy of glucocorticoids usually depends on dosage, although differences in sensitivity to glucocorticoids in individual animals have been reported. Glucocorticoids bind to the cytoplasmic glucocorticoid receptor (GR), which is expressed in almost all cells. These receptors are key factors in determining individual sensitivity to glucocorticoids. This study examined individual differences in glucocorticoid sensitivity in dogs, focusing on reactivity of the GR to prednisolone.ResultsWe first molecularly cloned the GR gene from a healthy dog. We discovered a mutant GR in a dog suspected to have iatrogenic Cushing syndrome. The mutant GR had extra nucleotides between exons 6 and 7, resulting in a truncated form of GR that was 98 amino acids shorter than the wild-type dog GR. The truncated GR exhibited very low reactivity to prednisolone, irrespective of concentration.ConclusionsWe have identified the truncated form of canine GR in a dog with iatrogenic Cushing syndrome. This truncated form showed the very less sensitivity to glucocorticoid in vitro, unfortunately, we could not elucidate its clinical significance. However, our data is a first report about the function of canine GR, and will facilitate the analysis of canine glucocorticoid sensitivity.
Highlights
Glucocorticoids, among the most widely utilized drugs in veterinary medicine, are employed to treat a wide variety of diseases; their use often induces adverse events in dogs
Clinical description of a dog suspected of having iatrogenic Cushing syndrome A 6-year-old spayed, mixed-breed dog was referred to the Yamaguchi University Animal Medical Center for detailed examination of skin disease
The dog was being treated for suspected iatrogenic Cushing syndrome, and its glucocorticoid receptor (GR) was characterized by a deletion, which was designated cGRΔLBD
Summary
Glucocorticoids, among the most widely utilized drugs in veterinary medicine, are employed to treat a wide variety of diseases; their use often induces adverse events in dogs. The efficacy of glucocorticoids usually depends on dosage, differences in sensitivity to glucocorticoids in individual animals have been reported. Glucocorticoids bind to the cytoplasmic glucocorticoid receptor (GR), which is expressed in almost all cells. These receptors are key factors in determining individual sensitivity to glucocorticoids. This study examined individual differences in glucocorticoid sensitivity in dogs, focusing on reactivity of the GR to prednisolone. The functions of glucocorticoids are initiated upon binding to the cytoplasmic glucocorticoid receptor (GR), Compared with humans, domesticated dogs and cats are relatively resistant to glucocorticoids [6]. We identified structural defects in the GR of the dog undergoing veterinary treatment and determined the GR sensitivity in this dog
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