English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/124519
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


Placenta passage of the thyroid hormone analog DITPA to male wild-type and Mct8-deficient mice

AuthorsFerrara, Alfonso M.; Gil-Ibáñez, Pilar CSIC; Bernal, Juan CSIC ORCID; Refetoff, Samuel
Issue Date2014
PublisherEndocrine Society
CitationEndocrinology 155(10): 4088-4093 (2014)
AbstractMonocarboxylate transporter 8 (MCT8) deficiency causes severe X-linked intellectual and neuropsychological impairment associated with abnormal thyroid function tests (TFTs) producing thyroid hormone (TH) deprivation in brain and excess in peripheral tissues. The TH analog diiodothyropropionic acid (DITPA) corrected the TFTs abnormalities and hypermetabolism of MCT8- deficient children but did not improve the neurological phenotype. The latter result was attributed to the late initiation of treatment. Therefore, we gave DITPA to pregnant mice carrying Mct8- deficient embryos to determine whether DITPA, when given prenatally, crosses the placenta and affects the serum TFTs and cerebral cortex of embryos. After depletion of the endogenous TH, Mct8-heterozygous pregnant dams carrying both wild-type (Wt) and Mct8-deficient (Mct8KO) male embryos were given DITPA. Effects were compared with those treated with levothyroxine (L-T4). With DITPA treatment, serum DITPA concentration was not different in the two genotypes, which produced equal effect on serum TSH levels in both groups of pups. In contrast, with L-T4treatment, TSH did not normalize in Mct8KO pups whereas it did in the Wt littermates and dams despite higher concentration of serum T4. Finally, both treatments similarly modulated the expression of the TH-dependent genes Shh, Klf9, and Aldh1a3 in brain. Thus, the ability of DITPA to cross the placenta, its thyromimetic action on the expression of TH-dependent genes in brain, and its better accessibility to the pituitary than L-T4, as assessed by serum TSH, make DITPA a candidate for the prenatal treatment of MCT8 deficiency.
Descriptionet al.
Identifiersdoi: 10.1210/en.2014-1085
issn: 0013-7227
e-issn: 1945-7170
Appears in Collections:(IIBM) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.