RESUMEN
OBJECTIVES: Pituitary-dependent hyperadrenocorticism is the most common cause of naturally occurring hypercortisolism in dogs. CRHR1 expression in human and dog corticotrophinomas suggested that this gene affects pituitary tumorigenesis. The present study aimed to investigate mutations in the CRHR1 coding region in poodles with pituitary-dependent hyperadrenocorticism. METHODS: Fifty poodles with pituitary-dependent hyperadrenocorticism and 50 healthy poodles were studied. Genomic DNA was amplified by PCR and analyzed by Sanger sequencing. RESULTS: The novel CRHR1 p.V97M mutation was identified in one dog. This valine residue, located in the amino-terminal extracellular domain, exhibits high affinity for its corticotropin-releasing hormone (CRH) ligand. Bioinformatic analysis revealed structural rearrangements in the mutant protein, with a 17% increase in the surface binding affinity between CRHR1 and CRH. In vitro functional studies showed that mutant CRHR1 induced higher ACTH secretion than the wild type after stimulation with human CRH. CONCLUSION: These results suggest that germline activating mutations in CRHR1 may be a rare cause of pituitary hyperadrenocorticism in poodles.
Asunto(s)
Animales , Masculino , Femenino , Perros , Mutación , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/veterinaria , Receptores de Hormona Liberadora de Corticotropina/genética , Hormona Adrenocorticotrópica/análisis , Análisis de Varianza , Estudios de Casos y Controles , Estudios de Asociación Genética/veterinaria , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/genética , Hipófisis/metabolismo , Reacción en Cadena de la Polimerasa/veterinaria , Estudios Prospectivos , Análisis de Secuencia de ADN/veterinaria , Factores de TiempoRESUMEN
It has been shown that there is an association between air pollution and cardiovascular mortality. In bone pathology, studies show that air pollution is associated with a risk of developing osteoporosis and osteoporotic fracture associated with MP2.5 and nitrogen dioxide (NO2 ). The aim of our study was to determine whether or not there is an association between air pollution and osteoporotic disease, associating the incidence of femoral neck fracture in individuals aged 50 years or more and the contamination present in the several cities. Our results showed no statistically significant association between air pollution, evaluated using PM10 and PM2.5 as indicators, and the average annual incidence of osteoporotic hip fracture, comparing the most polluted cities and the less polluted cities of Chile