Nuclear tri-iodothyronine (T3) binding in neonatal rat brain suggests a direct glial requirement for T3 during development

Abstract

ABSTRACT Tri-iodothyronine (T3) binding studies were performed on neuronal and glial nuclei prepared from developing rats brain by discontinuous sucrose gradient centrifugation. Maximum binding capacities (MBC) and dissociation constants (Kd) were obtained from Eadie-Hofstee plots of transformed data. An ontogenic study on nuclei prepared from whole brain revealed that on day 5 after birth, glial nuclear MBC was 1774±201 (s.e.m.) fmol/mg DNA compared with 974±117 fmol/mg DNA for the neurones (P<0·01). Although diminishing to 667±112 fmol/mg DNA by day 21, alterations in neuronal MBC over the neonatal period were not statistically significant, whereas glial MBC diminished steadily to 557±133 fmol/mg DNA in glial nuclei (P<0·05). Over the same period, a significant reduction in Kd was noted only in the glia, from 3·17±0·40 to 1·83±0·34 nmol/l (P<0·03). Ligand specificity of the receptor in both nuclear types on day 21 was tri-iodoacetic acid > T3 > thyroxine > 3,3′,5′-T3, but this was less clearly demonstrated at day 5. Regional studies on days 15 and 21 demonstrated that for both neuronal and glial nuclei, receptors are concentrated in the cerebral cortex and diminish in a cranio-caudal direction. Cerebral glial MBC on day 21 was 2215±147 fmol/mg DNA, at this stage still exceeding the cerebral neuronal capacity of 1111±207fmol/mg DNA. The results indicate that neonatal glia may respond directly to thyroid hormones via nuclear receptor binding, and that receptors are predominantly located in the cortex. Decreases in average MBC in the late neonate may be due to increases in the numbers of cells containing fewer nuclear receptors. Journal of Endocrinology (1990) 126, 409–415