Profiles of Steroid Hormones in Canine X-Linked Muscular Dystrophy via Stable Isotope Dilution LC-MS/MS

Autor(es)

Martins-Junior, Helio A. ^{[1, 2]} ; Simas, Rosineide C. ^{[1, 3]} ; Brolio, Marina P. ^[4] ; Ferreira, Christina R. ^{[1, 5]} ; Perecin, Felipe ^[4] ; Nogueira, Guilherme de P. ^[3] ; Miglino, Maria A. ^[6] ; Martins, Daniele S. ^[4] ; Eberlin, Marcos N. ^[1] ; Ambrosio, Carlos E. ^[4]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Inst Chem, ThoMSon Mass Spectrometry Lab, Campinas, SP - Brazil

^[2] AB SCIEX Brazil, Sao Paulo, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Fac Vet Med, DAPSA, Aracatuba, SP - Brazil

^[4] Univ Sao Paulo, FZEA, Pirassununga, SP - Brazil

^[5] Purdue Univ, Dept Chem, W Lafayette, IN 47907 - USA

^[6] Univ Sao Paulo, Fac Vet Med & Anim Sci FMVZ, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 5 MAY 26 2015.
• Citações Web of Science: 4

Resumo

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. (AU)

• Processo FAPESP: 10/51677-2 - Técnicas modernas em espectrometria de massas e desenvolvimento de novas aplicações em ciências: química, bioquímica, materiais, forense, medicina, alimentos, farmácia e veterinária
• Beneficiário: Marcos Nogueira Eberlin
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 07/51222-2 - Interação de terapia celular e gênica para a correção da distrofia muscular de Duchenne utilizando endonucleases quiméricas
• Beneficiário: Carlos Eduardo Ambrósio
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 10/15167-0 - Desenvolvimento e Validação Analítica de Método de Quantificação Simultânea de Estradiol e Progesterona por LC-MS/MS em Soro/Plasma Sanguíneo Bovino
• Beneficiário: Rosineide Costa Simas
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado