Journal article

Authors list: Gramer, I; Karakus, E; Hartmann, MF; Wudy, SA; Bauer, N; Moritz, A; Aktürk, Z; Geyer, J

Publication year: 2022

Pages: 265-272

Journal: Journal of Veterinary Pharmacology and Therapeutics

Volume number: 45

Issue number: 3

ISSN: 0140-7783

eISSN: 1365-2885

Open access status: Green

DOI Link: https://doi.org/10.1111/jvp.13050

Publisher: Wiley

Abstract: 
P-glycoprotein (P-gp) is the gene product of the multidrug resistance gene (MDR1, syn. ABCB1) that normally restricts the transfer of cortisol across the blood-brain barrier. In the absence of P-gp, cortisol access to the hypothalamus is increased and, by feedback inhibition, this finally leads to lower endogenous plasma cortisol levels in dogs with homozygous nt230(del4) MDR1 mutation (MDR1(-/-) mutant dogs). While a previous study only focused on plasma cortisol levels, the present study used urinary steroid hormone metabolites to analyze cortisol metabolism in MDR1(-/-) mutant dogs. Morning void urine was collected from 23 MDR1(-/-) mutant and 16 MDR1(+/+) normal dogs and was subjected to targeted GC-MS steroid hormone metabolome analysis. Seven cortisol metabolites, cortisol itself, and 13 other steroid metabolites were detected. In general, all cortisol metabolites were lower in the urine of the MDR1(-/-) mutant dogs, with allo-tetrahydro-cortisol and beta-cortol reaching the level of significance. In addition, 11-keto-pregnanetriol levels were significantly lower in the urine of the MDR1(-/-) mutant dogs, indicating that also the 17alpha-OH-progesterone-derived metabolism was altered. In conclusion, the present study provides the first steroid hormone metabolome analysis in the urine of MDR1(-/-) mutant dogs. Significant differences in the steroid metabolome of MDR1(-/-) mutant dogs point to a significant role of P-gp for cortisol metabolism and excretion and so indirectly also for hypothalamic-pituitary-adrenal axis regulation in dogs.

Harvard Citation style: Gramer, I., Karakus, E., Hartmann, M., Wudy, S., Bauer, N., Moritz, A., et al. (2022) Urinary cortisol metabolites are reduced in MDR1 mutant dogs in a pilot targeted GC-MS urinary steroid hormone metabolome analysis, Journal of Veterinary Pharmacology and Therapeutics, 45(3), pp. 265-272. https://doi.org/10.1111/jvp.13050

APA Citation style: Gramer, I., Karakus, E., Hartmann, M., Wudy, S., Bauer, N., Moritz, A., Aktürk, Z., & Geyer, J. (2022). Urinary cortisol metabolites are reduced in MDR1 mutant dogs in a pilot targeted GC-MS urinary steroid hormone metabolome analysis. Journal of Veterinary Pharmacology and Therapeutics. 45(3), 265-272. https://doi.org/10.1111/jvp.13050