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Lack of Effect of Thyroid Hormone on Late Fetal Rat Brain Development¹

Thyroid Research Unit, Division of Diabetes, Endocrinology, and Metabolism, Departments of Medicine (H.L.S., J.H.O.), Cell Biology and Neuroanatomy (H.L.S., J.H.O.), and Neurology (M.E.R.), University of Minnesota Medical School, Minneapolis, Minnesota 55455

Address all correspondence and requests for reprints to: Jack H. Oppenheimer, M.D., University of Minnesota, Box 91-UMHC, 420 Delaware Street Southeast, Minneapolis, Minnesota 55455. E-mail: oppen001{at}maroon.tc.umn.edu

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.

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