Triiodothyronine regulated tubulin biosynthesis in oligodendrocytes during myelinogenesis

Abstract

L-Triiodothyronine (T₃) is shown to stimulate the biosynthesis of tubulin in oligodendrocytes isolated from rat brains at different stages of myelinogenesis. The hormone sensitivity appears around day 11, reaches a maximum at day 15 and disappears by day 25 after birth. Dose response studies show that the optimal stimulation of tubulin in the oligodendrocytes from 15 day rat brain occurs with 0.045 nM T₃ in contrast to 4.5 nM T₃ that was previously shown to promote a similar age-dependent induction of tubulin in the astroglial cells from neonatal rat brain. Exposure of the oligodendrocytes to optimal dose of T₃ (0.045 nM) for 2 h elicits a marked and almost selective increase in the level of tubulin. Higher concentrations of T₃ induce additional proteins resulting in a loss of this sensitivity. Studies on the synthesis and turnover of ³⁵S-labeled tubulin show that the stimulation of tubulin by T₃ is primarily due to enhanced synthesis of the protein. Pulse chase experiments reveal that the half life of tubulin is about 5.5 h and that it remains unaffected by T₃. The crucial role of thyroid hormones and the possible function of tubulin in the two most critical phases of brain maturation viz. synaptogenesis and myelinogenesis is discussed.