Temperature Modulation of Glucocorticoid-receptor Affinity in a Hibernator, the European Ground Squirrel, and a Non-Hibernator, the Rat

  • Dragoslava Živadinović
  • Željko Džakula
  • Radoslav K. Andjus
Conference paper

Abstract

The time course of the specific binding of triamcinolone acetonide (a synthetic glucocorticoid) to its cytoplasmic receptor (rat and ground squirrel liver cytosol preparations) has been recorded at a series of incubation temperatures, from 0 to 37°C. Experimental results were fitted with a theoretical model accounting for the temperature dependence of complex formation and dissociation. A pronounced instability of the hormone-receptor complex was noted at relatively high incubation temperatures. Binding maxima formed bell-shaped temperature dependence profiles, peaking at a considerably lower temperature in the hibernator. A detailed study of the temperature dependence of the equilibrium dissociation constant (KD) showed that, with both preparations, KD values substantially increased with increasing temperature above 15°C (“positive temperature modulation of affinity”). A U-shaped temperature profile of the dissociation constant (KD), with its minimum at about 10°C, was obtained with preparations from the hibernator. Empirical data agreed completely with theoretical predictions, suggesting that the observed thermal modulation of affinity might be a direct consequence of intrinsic kinetic properties of steroid-receptor interactions. In the case of the rat, however, empirical data points deviated appreciably from model-predictions in the low temperature region, forming a“J”-type plot rather than the predicted U-shape profile. The lowest KD value was situated at about 15°C, five degrees above the hibernator’s KD inversion temperature. In the case of both species, temperatures characterized by the smallest KD values (greatest hormone-receptor affinity) were close to body temperatures representing temperature limits of spontaneous recovery from induced hypothermia.

Keywords

Entropy Enthalpy Lactate Cage Pyruvate 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Dragoslava Živadinović
    • 1
  • Željko Džakula
    • 2
  • Radoslav K. Andjus
    • 3
  1. 1.NICHD, ERRB, NIHBethesdaUSA
  2. 2.Molecular Simulations Inc.San DiegoUSA
  3. 3.Center for Multidisciplinary StudiesUniversity of BelgradeBelgradeYugoslavia

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