{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:39:34Z","timestamp":1789763974269,"version":"4.0.1"},"reference-count":20,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Monocarboxylate 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-T4 treatment, 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.<\/jats:p>","DOI":"10.1210\/en.2014-1085","type":"journal-article","created":{"date-parts":[[2014,7,22]],"date-time":"2014-07-22T17:27:33Z","timestamp":1406050053000},"page":"4088-4093","source":"Crossref","is-referenced-by-count":25,"title":["Placenta Passage of the Thyroid Hormone Analog DITPA to Male Wild-Type and Mct8-Deficient Mice"],"prefix":"10.1210","volume":"155","author":[{"given":"Alfonso Massimiliano","family":"Ferrara","sequence":"first","affiliation":[{"name":"Departments of Medicine (A.M.F., X.-H.L., P.G.-I., R.E.W., A.M.D., S.R.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hui","family":"Liao","sequence":"first","affiliation":[{"name":"Departments of Medicine (A.M.F., X.-H.L., P.G.-I., R.E.W., A.M.D., S.R.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Gil-Ib\u00e1\u00f1ez","sequence":"first","affiliation":[{"name":"Departments of Medicine (A.M.F., X.-H.L., P.G.-I., R.E.W., A.M.D., S.R.), The University of Chicago, Chicago, Illinois 60637"},{"name":"Instituto de Investigaciones Biom\u00e9dicas and Center for Biomedical Research on Rare Diseases (P.G-I., J.B.), Consejo Superior de Investigaciones Cient\u00edficas and Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Bernal","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas and Center for Biomedical Research on Rare Diseases (P.G-I., J.B.), Consejo Superior de Investigaciones Cient\u00edficas and Universidad Aut\u00f3noma de Madrid, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy E.","family":"Weiss","sequence":"first","affiliation":[{"name":"Departments of Medicine (A.M.F., X.-H.L., P.G.-I., R.E.W., A.M.D., S.R.), The University of Chicago, Chicago, Illinois 60637"},{"name":"Pediatrics (R.E.W., S.R.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra M.","family":"Dumitrescu","sequence":"first","affiliation":[{"name":"Departments of Medicine (A.M.F., X.-H.L., P.G.-I., R.E.W., A.M.D., S.R.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Refetoff","sequence":"first","affiliation":[{"name":"Departments of Medicine (A.M.F., X.-H.L., P.G.-I., R.E.W., A.M.D., S.R.), The University of Chicago, Chicago, Illinois 60637"},{"name":"Pediatrics (R.E.W., S.R.), The University of Chicago, Chicago, Illinois 60637"},{"name":"The Committee on Genetics (S.R.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612052473700_B1","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.1210\/en.2006-0390","article-title":"Tissue-specific thyroid hormone deprivation and excess in monocarboxylate transporter (mct) 8-deficient mice","volume":"147","author":"Dumitrescu","year":"2006","journal-title":"Endocrinology"},{"key":"2020071612052473700_B2","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1172\/JCI28253","article-title":"Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8","volume":"117","author":"Trajkovic","year":"2007","journal-title":"J Clin Invest"},{"key":"2020071612052473700_B3","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0083-6729(05)71004-9","article-title":"Thyroid hormones and brain development","volume":"71","author":"Bernal","year":"2005","journal-title":"Vitam Horm"},{"key":"2020071612052473700_B4","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1016\/j.bbagen.2012.08.005","article-title":"The syndromes of reduced sensitivity to thyroid hormone","volume":"1830","author":"Dumitrescu","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"2020071612052473700_B5","doi-asserted-by":"crossref","first-page":"4885","DOI":"10.1210\/en.2013-1150","article-title":"Mct8-deficient mice have increased energy expenditure and reduced fat mass that is abrogated by normalization of serum T3 levels","volume":"154","author":"Di Cosmo","year":"2013","journal-title":"Endocrinology"},{"key":"2020071612052473700_B6","doi-asserted-by":"crossref","first-page":"4450","DOI":"10.1210\/en.2009-0209","article-title":"A thyroid hormone analog with reduced dependence on the monocarboxylate transporter 8 for tissue transport","volume":"150","author":"Di Cosmo","year":"2009","journal-title":"Endocrinology"},{"key":"2020071612052473700_B7","doi-asserted-by":"crossref","first-page":"4515","DOI":"10.1210\/jc.2012-2556","article-title":"Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency","volume":"97","author":"Verge","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612052473700_B8","doi-asserted-by":"crossref","first-page":"4362","DOI":"10.1210\/jc.2012-3759","article-title":"Finding the way into the brain without MCT8","volume":"97","author":"Visser","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612052473700_B9","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1097\/01.med.0000432531.03233.ad","article-title":"Inherited defects of thyroid hormone-cell-membrane transport: Review of recent findings","volume":"20","author":"Fu","year":"2013","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"2020071612052473700_B10","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1210\/en.2012-2031","article-title":"Changes in thyroid status during perinatal development of MCT8-deficient male mice","volume":"154","author":"Ferrara","year":"2013","journal-title":"Endocrinology"},{"key":"2020071612052473700_B11","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1210\/en.2010-1014","article-title":"Lack of action of exogenously administered T3 on the fetal rat brain despite expression of the monocarboxylate transporter 8","volume":"152","author":"Grijota-Mart\u00ednez","year":"2011","journal-title":"Endocrinology"},{"key":"2020071612052473700_B12","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1210\/mend.11.11.9915","article-title":"Purification, molecular cloning, and functional expression of the human nicodinamide-adenine dinucleotide phosphate-regulated thyroid hormone-binding protein","volume":"11","author":"Vi\u00e9","year":"1997","journal-title":"Mol Endocrinol"},{"key":"2020071612052473700_B13","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1210\/en.2012-1628","article-title":"Tetrac can replace thyroid hormone during brain development in mouse mutants deficient in the thyroid hormone transporter mct8","volume":"154","author":"Horn","year":"2013","journal-title":"Endocrinology"},{"key":"2020071612052473700_B14","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1210\/jc.2007-2719","article-title":"Beneficial effects of propylthiouracil plus L-thyroxine treatment in a patient with a mutation in MCT8","volume":"93","author":"W\u00e9meau","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612052473700_B15","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1590\/S0004-27302011000100008","article-title":"Novel mutation in MCT8 gene in a Brazilian boy with thyroid hormone resistance and severe neurologic abnormalities","volume":"55","author":"Filho","year":"2011","journal-title":"Arq Bras Endocrinol Metabol"},{"key":"2020071612052473700_B16","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/cen.12023","article-title":"Identification, functional analysis, prevalence and treatment of monocarboxylate transporter 8 (MCT8) mutations in a cohort of adult patients with mental retardation","volume":"78","author":"Visser","year":"2013","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071612052473700_B17","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1530\/EJE-11-0358","article-title":"A child with a deletion in the monocarboxylate transporter 8 gene: 7-year follow-up and effects of thyroid hormone treatment","volume":"165","author":"Zung","year":"2011","journal-title":"Eur J Endocrinol"},{"key":"2020071612052473700_B18","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/BF03349663","article-title":"Neonatal hepatitis and lymphocyte sensitization by placental transfer of propylthiouracil","volume":"13","author":"Hayashida","year":"1990","journal-title":"J Endocrinol Invest"},{"key":"2020071612052473700_B19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000336071","article-title":"A Case of Propylthiouracil-Induced Hepatitis during Pregnancy","volume":"1","author":"Taylor","year":"2012","journal-title":"Eur Thyroid J"},{"key":"2020071612052473700_B20","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1089\/thy.2012.0488","article-title":"Prevalence of thyrotoxicosis, antithyroid medication use, and complications among pregnant women in the United States","volume":"23","author":"Korelitz","year":"2013","journal-title":"Thyroid"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/155\/10\/4088\/10827494\/endo4088.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/155\/10\/4088\/10827494\/endo4088.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T18:56:54Z","timestamp":1594925814000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/155\/10\/4088\/2423693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,1]]},"references-count":20,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2014,10,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2014-1085","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,1]]}}}