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15 results on '"Iglesias-Osma, Maria Carmen"'

7. Intranasal delivery of thyroid hormones in MCT8 deficiency

Author

Iglesias Osma, Maria Carmen, Grijota Martínez, María Carmen, Bárez López, Soledad, Ausó, Eva, Refetoff, Samuel, Frey, William H., Guadaño Ferraz, Ana, Iglesias Osma, Maria Carmen, Grijota Martínez, María Carmen, Bárez López, Soledad, Ausó, Eva, Refetoff, Samuel, Frey, William H., and Guadaño Ferraz, Ana

Abstract

Loss of function mutations in the gene encoding the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to severe neurodevelopmental defects in humans associated with a specific thyroid hormone phenotype manifesting high serum 3,5,3'-triiodothyronine (T3) and low thyroxine (T4) levels. Patients present a paradoxical state of peripheral hyperthyroidism and brain hypothyroidism, this last one most likely arising from impaired thyroid hormone transport across the brain barriers. The administration of thyroid hormones by delivery pathways that bypass the brain barriers, such as the intranasal delivery route, offers the possibility to improve the neurological defects of MCT8-deficient patients. In this study, the thyroid hormones T4 and T3 were administrated intranasally in different mouse models of MCT8 deficiency. We have found that, under the present formulation, intranasal administration of thyroid hormones does not increase the content of thyroid hormones in the brain and further raises the peripheral thyroid hormone levels. Our data suggests intranasal delivery of thyroid hormones is not a suitable therapeutic strategy for MCT8 deficiency, although alternative formulations could be considered in the future to improve the nose-to-brain transport., Ministerio de Economía y Competitividad (España), Sherman Foundation, Biotechnology and Biological Sciences Research Council (UK), Instituto de Salud Carlos III., National Institutes of Health (USA), Depto. de Biología Celular, Fac. de Ciencias Biológicas, TRUE, pub

Published
2020

13. Sequential testicular atrophy involves changes in cellular proliferation and apoptosis associated with variations in aromatase P450 expression levels in Irs-2-deficient mice

Author

Catalano-Iniesta, Leonardo, primary, Sánchez-Robledo, Virginia, additional, Iglesias-Osma, Maria Carmen, additional, García-Barrado, Maria José, additional, Carretero-Hernández, Marta, additional, Blanco, Enrique J., additional, Vicente-García, Teresa, additional, Burks, Deborah Jane, additional, and Carretero, José, additional

Published
2018
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14. Sequential testicular atrophy involves changes in cellular proliferation and apoptosis associated with variations in aromatase P450 expression levels in Irs‐2‐deficient mice.

Author

Catalano‐Iniesta, Leonardo, Sánchez‐Robledo, Virginia, Iglesias‐Osma, Maria Carmen, García‐Barrado, Maria José, Carretero‐Hernández, Marta, Blanco, Enrique J., Vicente‐García, Teresa, Burks, Deborah Jane, and Carretero, José

Subjects
CELL proliferation, APOPTOSIS, ATROPHY, AROMATASE, LABORATORY mice, TESTIS, MAMMALS
Abstract

Insulin receptor substrate 2 (Irs‐2) is an intracellular protein susceptible to phosphorylation after activation of the insulin receptor. Its suppression affects testis development and its absence induces peripheral resistance to insulin. The aim of this study was to identify changes induced by the deletion of Irs‐2 in the testicular structure and by the altered expression of cytochrome P450 aromatase, a protein necessary for the development and maturation of germ cells. Adult knockout (KO) mice (Irs‐2−/−, 6 and 12 weeks old) and age‐matched wild‐type (WT) mice were used in this study. Immunohistochemistry and Western blot analyses were performed to study proliferation (PCNA), apoptosis (active caspase‐3) and P450 aromatase expression in testicular histological sections. Deletion of Irs‐2 decreased the number of epithelial cells in the seminiferous tubule and rete testis. Aberrant cells were frequently detected in the epithelia of Irs‐2−/− mice, accompanied by variations in spermatogonia, which were shown to exhibit small hyperchromatic nuclei as well as polynuclear and anuclear structures. The amount of cell proliferation was significantly lower in Irs‐2−/− mice than in WT mice, whereas apoptotic processes were more common in Irs‐2−/− mice. Aromatase P450 reactivity was higher in 6‐week‐old KO mice than in WT mice of the same age and was even higher at 12 weeks. Our results suggest that Irs‐2 is a key element in spermatogenesis because silencing Irs‐2 induces the sequential development of testicular atrophy. The effects are observed mainly in germ cells present in the seminiferous tubule, which may be due to changes in cytochrome P450 aromatase expression. [ABSTRACT FROM AUTHOR]

Published
2019
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