Abstract
Golden retriever muscular dystrophy (GRMD) provides the best animal model for characterizing the disease progress of the human disorder, Duchenne muscular dystrophy (DMD). The purpose of this study was to determine steroid hormone concentration profiles in healthy golden retriever dogs (control group - CtGR) versus GRMD-gene carrier (CaGR) and affected female dogs (AfCR). Therefore, a sensitive and specific analytical method was developed and validated to determine the estradiol, progesterone, cortisol, and testosterone levels in the canine serum by isotope dilution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). To more accurately understand the dynamic nature of the serum steroid profile, the fluctuating levels of these four steroid hormones over the estrous cycle were compared across the three experimental groups using a multivariate statistical analysis. The concentration profiles of estradiol, cortisol, progesterone, and testosterone revealed a characteristic pattern for each studied group at each specific estrous phase. Additionally, several important changes in the serum concentrations of cortisol and estradiol in the CaGR and AfCR groups seem to be correlated with the status and progression of the muscular dystrophy. A comprehensive and quantitative monitoring of steroid profiles throughout the estrous cycle of normal and GRMD dogs were achieved. Significant differences in these profiles were observed between GRMD and healthy animals, most notably for estradiol. These findings contribute to a better understanding of both dog reproduction and the muscular dystrophy pathology. Our data open new venues for hormonal behavior studies in dystrophinopathies and that may affect the quality of life of DMD patients.
Highlights
Golden retriever dogs are affected by a degenerative muscle disease that is genetically homologous to Duchenne muscular dystrophy (DMD) in humans and are commonly used as an animal model for this disease
The principal aim of the current study was to develop the first specific LC-MS/MS assay for the quantification of progesterone, estradiol, cortisol, and testosterone in dogs
The motivation for this goal was the importance of precision and the confident quantification of steroid hormones in dogs for understanding the reproductive changes observed in golden retriever muscular dystrophy (GRMD) animals
Summary
Golden retriever dogs are affected by a degenerative muscle disease that is genetically homologous to Duchenne muscular dystrophy (DMD) in humans and are commonly used as an animal model for this disease. Golden retriever muscular dystrophy (GRMD) affects the expression of the dystrophin gene, which codes for a cytoskeletal protein and results in a weakening of the musculoskeletal system and impaired locomotion. Changes in steroid hormone levels in GRMD dogs compared with healthy dogs are unknown. This information may be crucial for further research into the effect of this dystrophin deletion on the physiology of these animals
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