{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:04:50Z","timestamp":1771232690626,"version":"3.50.1"},"reference-count":29,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,11,1]]},"abstract":"<jats:p>A level of thyroid hormone (TH) in agreement with the tissue requirements is essential for vertebrate embryogenesis and fetal maturation. In this study we evaluate the immediate and long-term effects of incongruent intrauterine TH levels between mother and fetus using the TH receptor (TR) \u03b2\u2212\/\u2212 knockout mouse as a model. We took advantage of the fact that the TR\u03b2\u2212\/\u2212 females have elevated serum TH but are not thyrotoxic due to resistance to TH. We used crosses between heterozygotes with wild-type phenotype (TR\u03b2+\/\u2212) males and TR\u03b2\u2212\/\u2212 females, with a hyperiodothyroninemic (high T4 and T3 levels) intrauterine environment (TH congruent with the TR\u03b2\u2212\/\u2212 fetus and excessive for the TR\u03b2+\/\u2212 fetus), and reciprocal crosses between TR\u03b2\u2212\/\u2212 males and TR\u03b2+\/\u2212 females, providing a euiodothyroninemic intrauterine environment. We found that TR\u03b2\u2212\/\u2212 dams had reduced litter sizes and pups with lower birth weight but preserved the mendelian TR\u03b2\u2212\/\u2212 to TR\u03b2+\/\u2212 ratio at birth, indicating that the incongruous TH levels did not decrease intrauterine survival of a specific genotype. The results of studies in newborns demonstrate that TR\u03b2+\/\u2212 pups born to TR\u03b2\u2212\/\u2212 dams have persistent suppression of serum TSH without a peak. On the other hand, TR\u03b2\u2212\/\u2212 pups born to TR\u03b2+\/\u2212 dams have lower serum TSH at birth and a tendency to peak higher, compared with TR\u03b2\u2212\/\u2212 pups born to TR\u03b2\u2212\/\u2212 dams. The studies in the adult progeny demonstrate that TR\u03b2+\/\u2212 mice born to TR\u03b2\u2212\/\u2212 dams and, thus, exposed to higher intrauterine TH levels, have greater resistance to TH at the level of the pituitary when stimulated with TRH. On the other hand, TR\u03b2\u2212\/\u2212 mice born to TR\u03b2+\/\u2212 dams and, thus, deprived of TH in uterine life, were more sensitive to TH when similarly stimulated with TRH. Thus, TH exposure in utero has an effect on the regulatory set point of the hypothalamus-pituitary-thyroid axis, which can be seen early in life and persists into adulthood.<\/jats:p>","DOI":"10.1210\/en.2007-0677","type":"journal-article","created":{"date-parts":[[2007,8,10]],"date-time":"2007-08-10T00:35:28Z","timestamp":1186706128000},"page":"5305-5312","source":"Crossref","is-referenced-by-count":25,"title":["Effects of Maternal Levels of Thyroid Hormone (TH) on the Hypothalamus-Pituitary-Thyroid Set Point: Studies in TH Receptor \u03b2 Knockout Mice"],"prefix":"10.1210","volume":"148","author":[{"given":"Manuela","family":"Alonso","sequence":"first","affiliation":[{"name":"Department of Medicine (M.A., C.G., X.L., D.P., S.R., R.E.W.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Goodwin","sequence":"additional","affiliation":[{"name":"Department of Medicine (M.A., C.G., X.L., D.P., S.R., R.E.W.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"XiaoHui","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Medicine (M.A., C.G., X.L., D.P., S.R., R.E.W.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Page","sequence":"additional","affiliation":[{"name":"Department of Medicine (M.A., C.G., X.L., D.P., S.R., R.E.W.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Refetoff","sequence":"additional","affiliation":[{"name":"Department of Medicine (M.A., C.G., X.L., D.P., S.R., R.E.W.), The University of Chicago, Chicago, Illinois 60637"},{"name":"Department of Pediatrics (S.R., R.E.W.), The University of Chicago, Chicago, Illinois 60637"},{"name":"Department of Committees on Genetics (S.R.), The University of Chicago, Chicago, Illinois 60637"},{"name":"Department of Molecular Medicine (S.R., R.E.W.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy E.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Medicine (M.A., C.G., X.L., D.P., S.R., R.E.W.), The University of Chicago, Chicago, Illinois 60637"},{"name":"Department of Pediatrics (S.R., R.E.W.), The University of Chicago, Chicago, Illinois 60637"},{"name":"Department of Molecular Medicine (S.R., R.E.W.), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071613454478800_R1","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1056\/NEJM199410203311608","article-title":"Maternal and fetal thyroid function.","volume":"331","author":"Burrows","year":"1994","journal-title":"N Engl J 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