Lack of effect of thyroid hormone on late fetal rat brain development.
Studies were undertaken to test whether alterations in fetal brain thyroid hormone levels during the final week of gestation can prematurely induce gene expression in brain or affect cerebellar morphogenesis. Pregnant dams were treated either by administration of 0.025% methimazole (MMI) in the drinking water from day 14 post conception (PC14) or administration of 2.5 mg T4/100 g BW on PC15. On PC21, treatment with MMI resulted in a 53% fall in fetal brain T3 levels and excess T4 resulted in a 2- to 3-fold increase to concentrations observed in adult brains. Neither excess nor reduced levels of T3 caused alterations in the expression of the myelin basic protein, Pcp-2 or calmodulin kinase IV genes. Cerebella of control brains showed early evidence of foliation and the presence of a several cell thick Purkinje cell layer and an external granule layer. No treatment induced effects were evident. Thus, at the late fetal stage in the rat, the developing brain appears to be unresponsive to thyroid hormone despite the presence of thyroid hormone receptors. We infer the presence of as yet unidentified factors that suppress precocious response to thyroid hormone or the absence of cofactors essential for such a response.
Schwartz
H L
HL
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.
Ross
M E
ME
Oppenheimer
J H
JH
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D015152:Blotting, Northern; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D001923:Brain Chemistry; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D008713:Methimazole / Q000494:pharmacology; D004676:Myelin Basic Protein / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D009929:Organ Size; D011247:Pregnancy; D012313:RNA / Q000032:analysis; D051381:Rats; D013963:Thyroid Hormones / Q000494:pharmacology*; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology
D013956:Antithyroid Agents; D004676:Myelin Basic Protein; D013963:Thyroid Hormones; D014284:Triiodothyronine; D008713:Methimazole; D012313:RNA; D004247:DNA; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517686:Camk4 protein, rat; D013974:Thyroxine