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Nuclear Receptors for 3,5,3'-Triiodothyronine in Human Liver and Kidney: Characterization, Quantitation, and Similarities to Rat Receptors^*

LAWRENCE D. SCHUSTER, HAROLD L. SCHWARTZ and JACK H. OPPENHEIMER

Division of Endocrinology and Metabolism, Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455

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 (K_a) 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 K_a 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. (J Clin Endocrinol Metab 48: 627, 1979)

^* This work was supported by NIH Grant AM-19812-02. This study was performed in partial fulfillment of the thesis requirement for the award of the Ph.D. degree in Medicine by the Graduate Faculty of the University of Minnesota (L.D.S.).

Special Postdoctoral Fellow of the Leukemia Society.

Received July 18, 1978.