Dynamic nongenomic actions of thyroid hormone in the developing rat brain.
Two well-characterized nongenomic actions of thyroid hormone in cultured brain tissues are: 1) regulation of type 2 iodothyronine 5'deiodinase (D2) activity and 2) regulation of actin polymerization. In particular, the latter is likely to have profound effects on neuronal migration in the developing brain. In this study, we determined whether these nongenomic actions also occurred in vivo during brain development. Neonatal hypothyroidism was induced by propylthiouracil given to pregnant dams beginning on d17 of gestation and continued throughout the neonatal period. On postnatal d 14, rats were injected with either cold or [(125)I]-labeled iodothyronines and killed sequentially after injection. In contrast to reports in the adult rat, all three iodothyronines readily and equally entered developing brain tissues. As expected, cerebrocortical D2 activity was markedly elevated in the hypothyroid brain and both reverse T(3) (rT(3)) and T(4) rapidly decreased D2 to euthyroid levels within 3 h. Furthermore, cerebellar G-actin content in the hypothyroid rat was approximately 5-fold higher than in the euthyroid rat. Again, both rT(3) and T(4) rapidly decreased the G-actin content by approximately 50%, with a reciprocal increase in F-actin content to euthyroid levels without altering total actin. Neither T(3) nor vehicle had any effect on D2 activity in the cortex or G- or F-actin content in the cerebellum. The thyroid hormone-dependent regulation of actin polymerization in the rat brain provides a mechanism by which this morphogenic hormone can influence neuronal migration independent of the need for altered gene transcription. Furthermore, these data suggest a prominent role for rT(3) during brain development.
University of Massachusetts Medical School, Worcester, 01655, USA. alan.farwell@umassmed.edu
Alan P
AP
Farwell
Susan A
SA
Dubord-Tomasetti
Andrzej Z
AZ
Pietrzykowski
Jack L
JL
Leonard
D000199:Actins / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002465:Cell Movement; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007453:Iodide Peroxidase / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D013963:Thyroid Hormones / Q000378:metabolism*; D013997:Time Factors; D000097564:Iodothyronine Deiodinase Type II
D000199:Actins; D007453:Iodide Peroxidase; D013963:Thyroid Hormones; D000097564:Iodothyronine Deiodinase Type II