NUCLEAR AND CYTOPLASMIC TRIIODOTHYRONINE-BINDING SITES IN PRIMARY SENSORY NEURONS AND SCHWANN-CELLS - AUTORADIOGRAPHIC STUDY DURING DEVELOPMENT

The effects of the thyroid hormones on target cells are mediated throu gh nuclear T-3 receptors. In the peripheral nervous system, nuclear T- 3 receptors were previously detected with the monoclonal antibody 2B3 mAb in all the primary sensory neurons throughout neuronal life and in peripheral glia at the perinatal period only (Eur. J. Neurosci. 5, 31 9, 1993). To determine whether these nuclear T-3 receptors correspond to functional ones able to bind T-3, cryostat sections and in vitro ce ll cultures of dorsal root ganglion (DRG) or sciatic nerve were incuba ted with 0.1 nM [(125)l]-labeled T-3, either alone to visualize the to tal T-3-binding sites or added with a 10(3) fold excess of unlabeled T -3 to estimate the part due to the non-specific T-3-binding. After glu taraldehyde fixation, radioautography showed that the specific T-3-bin ding sites were largely prevalent. The T-3-binding capacity of periphe ral glia in DRG and sciatic nerve was restricted to the perinatal peri od in vivo and to Schwann cells cultured in vitro. In all the primary sensory neurons, specific T-3-binding sites were disclosed in foetal a s well as adult rats. The detection of the T-3-binding sites in the nu cleus indicated that the nuclear T-3 receptors are functional. Moreove r the concomitant presence of both T-3-binding sites and T(3)receptors a isoforms in the perikaryon of DRG neurons infers that: 1) [(125)l]- labeled T-3 can be retained on the T-3-binding 'E' domain of nascent a lpha(1) isoform molecules newly-synthesized on the perikaryal ribosome s; 2) the a isoforms translocated to the nucleus are modified by postt ranslational changes and finally recognized by 2B3 mAb as nuclear T-3 receptor. In conclusion, the radioautographic visualization of the T-3 -binding sites in peripheral neurons and glia confirms that the nuclea r T, receptors are functional and contributes to clarify the discordan t intracellular localization provided by the immunocytochemical detect ion of nuclear T-3 receptors and T-3 receptor alpha isoforms.