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Molecular Basis of Thyroid Hormone-Dependent Brain Development¹

Thyroid Research Unit, Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455

I. Introduction

II. Developmental Schedules

A. Species specificity

B. Developmental studies in the rat

III. Thyroid Hormone Action

A. Sources of T₄ and T₃

B. The role of maternal thyroid hormone in fetal brain development: direct or indirect?

C. Intracerebral transport

IV. Molecular Actions of Thyroid Hormone in the Developing Brain

A. Nuclear receptors for thyroid hormone in brain

B. Thyroid hormone receptor isoforms and their tissue distribution

C. Interactions of ligand, receptor, and DNA

D. Ontogeny of thyroid hormone receptor isoforms in brain

E. Search for T₃-responsive genes in the neonatal rat brain

F. Regulation of gene expression by T₃ through indirect molecular pathways?

G. Extranuclear actions of T₄?

V. Theories and Speculations

VI. Conclusions