DIFFERENTIAL DISTRIBUTION OF THYROID-HORMONE RECEPTOR ISOFORM IN RAT DORSAL-ROOT GANGLIA AND SCIATIC-NERVE IN-VIVO AND IN-VITRO

Using autoradiographic techniques carried out under precise conditions we previously demonstrated that both sensory neurons and peripheral g lial cells in dorsal root ganglia (DRG) or sciatic nerve, possess spec ific [I-125]-labeled T-3 binding sites. Thyroid hormone receptors (TR) include several isoforms (TR alpha(1), TR alpha(2), TRP beta(1), TR b eta(2).) The present study demonstrates that while sensory neurons and peripheral glial cells both possess functional Tn, they express a dif ferential expression of Tn isoforms. Using a panel of antisera to spec ific for the TR alpha-common (alpha(1) and alpha(2)), TR alpha-1 or TR beta-1 isoforms, we detected TRs isoform localization at the cellular level during DRG and sciatic nerve development and regeneration. Immu nohistochemical analysis revealed that during embryonic life, sensory neurons express TR alpha-common and TR beta-1 rather than TR alpha-1. The number of TR alpha-common and TR beta-1 positive neurons as well a s the intensity of labeling increased during the first two postnatal w eeks and remained more or less stable in adult life. TR alpha-1 immuno reactivity, which was undetectable in embryonic sensory neurons, becam e discreetly visible in neurons after birth. In developing DRG and sci atic nerves, Schwann cells exhibited TR alpha-common and TR alpha-1 ra ther than TR beta-1 immunolabeling. The appearance of TR alpha-common and alpha-1 isoform immunoreactivity in the sciatic nerve was restrict ed to a short period ranging from E17 up to two postnatal weeks. By co mparing TR alpha-common and TR alpha-1 immunostaining we can deduce th at Schwann cells primarily express TR alpha-1. Afterwards, in adult ra t sciatic nerve TR alpha isoforms was no more detected. However transe ction of sciatic nerve caused a reexpression of TR alpha isoforms in d egenerating nerve. The prevalence of TR alpha in Schwann cells in vivo was correlated with in vitro results. The differential expression of TR alpha and beta by sensory neurons and Schwann cells indicates that the feedback regulation of circulating thyroid hormone could occur by binding to either the alpha or beta TR isoforms. Moreover, the presenc e of multiple receptor isoforms in developing sensory neurons suggests that thyroid hormone uses multiple signaling pathways to regulate DRG and sciatic nerve development.