NUCLEAR RECEPTORS FOR 3,5,3'-TRIIODOTHYRONINE IN HUMAN-LIVER AND KIDNEY - CHARACTERIZATION, QUANTITATION, AND SIMILARITIES TO RAT RECEPTORS

Studies were undertaken to compare the T3-specific nuclear receptors from the liver and kidney of man and rat. Human liver was obtained from two male accident victims. Human kidney was taken from grossly normal areas of surgical specimens removed because of ureteral obstruction (n = 3) or hypernephroma (n = 2). Rat liver and kidney were obtained from Sprague-Dawley rats, weighing 150-250 g. Nuclei were purified through 2.4 M sucrose by methods previously described. Maximum binding capacity and affinity constants (Ka) were determined by incubation of whole nuclei at 37 C for 30 min with increasing concentrations of [125I]T3. Both rat and human tissues exhibited a single class of binding sites with a Ka of approximately 1 X 109 M‑1. The maximal binding capacities of the same tissue from both species were very similar (expressed as nanograms of T3 per mg DNA): human liver, 0.68; rat liver, 0.76; human kidney, 0.24; and rat kidney, 0.26. Endogenous T3 specifically bound to the nuclear receptors was measured by RIA of ethanolic extracts. Again, the values for each tissue were nearly identical (expressed as nanograms of T3 per mg DNA): human liver, 0.30; rat liver, 0.32; human kidney, 0.15; and rat kidney, 0.16. These data suggest that in the human, as in the rat, approximately 50% of the total nuclear sites are occupied at normal levels of plasma T3. Further evidence of the similarity of the nuclear receptors of the two species comes from the observation of the identity of their chromatographic mobility on DEAE-Sephadex A-50 and sedimentation properties on 5-20% sucrose gradients and the similarity in the spectrum of relative binding affinities of analogs of T3, including T4, triiodothyroacetic acid, 3'-isopropyl-3, 5-diiodothyronine, and rT3. Thus, by several independent criteria, nuclear receptors in man and rat appear nearly the same. Moreover, similarities in the association constant and in the fraction of nuclear sites occupied under physiological conditions suggest the kinetics of interchange between nuclear and plasma T3 are governed by the same physiological principles. © 1979 by The Endocrine Society.