Nuclear tri-iodothyronine (T3) binding in neonatal rat brain suggests a direct glial requirement for T3 during development.
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 less than 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 less than 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 less than 0.03). Ligand specificity of the receptor in both nuclear types on day 21 was tri-iodoacetic acid greater than T3 greater than thyroxine greater than 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 +/- 207 fmol/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Molecular Endocrinology, University College and Middlesex School of Medicine, London.
M
M
Hubank
A K
AK
Sinha
D
D
Gullo
R P
RP
Ekins
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000378:metabolism*
D014284:Triiodothyronine