Influence of Vitamin D Deficiency on Cyclin D1-Induced Parathyroid Tumorigenesis.
Primary hyperparathyroidism (PHPT) is a common endocrinopathy for which several pathogenic mechanisms, including cyclin D1 overexpression, have been identified. Vitamin D nutritional status may influence parathyroid tumorigenesis, but evidence remains circumstantial. To assess the potential influence of vitamin D insufficiency/deficiency on initiation or progression of parathyroid tumorigenesis, we superimposed vitamin D insufficiency or deficiency on parathyroid tumor-prone PTH-cyclin D1 transgenic mice. Mice were placed on diets containing either 2.75 IU/g, 0.25 IU/g, or 0.05 IU/g cholecalciferol, either prior to expected onset of PHPT or after onset of biochemical PHPT. When introduced early, superimposed vitamin D insufficiency/deficiency had no effect on serum calcium or on parathyroid gland growth. However, when introduced after the onset of biochemical PHPT, vitamin D deficiency led to larger parathyroid glands without differences in serum biochemical parameters. Our results suggest that low vitamin D status enhances proliferation of parathyroid cells whose growth is already being tumorigenically driven, in contrast to its apparent lack of direct proliferation-initiating action on normally growing parathyroid cells in this model. These results are consistent with the hypothesis that suboptimal vitamin D status may not increase incidence of de novo parathyroid tumorigenesis but may accelerate growth of a pre-existing parathyroid tumor.
Published In/Presented At
Costa-Guda, J., Corrado, K., Bellizzi, J., Saria, E., Saucier, K., Guemes-Aragon, M., Kakar, G., Rose, M., Pascal, M., Alander, C., Mallya, S. M., & Arnold, A. (2023). Influence of Vitamin D Deficiency on Cyclin D1-Induced Parathyroid Tumorigenesis. Endocrinology, bqad137. Advance online publication. https://doi.org/10.1210/endocr/bqad137
Medicine and Health Sciences
Department of Surgery