Depletion and Replenishment of Glucocorticoid Receptor in Cytosols of Rat Tissues after Administration of Various Glucocorticoids

Administration of steroid hormones evokes a rapid fall in the amount of cytoplasmic receptors in target tissues. This has been considered to be a consequence of the receptor translocation to nuclei, but the physiological significane of depletion of the cytoplasmic receptors after hormone administration has not been fully elucidated. In the present study, depletion and replenishment of the cytoplasmic glucocorticoid receptor in rat tissues were examined after the administration of glucocorticoids of different biological potencies. Dose dependent depletion was observed in all tissues examined and doses required for complete depletion of the receptor were correlated with biological potencies of steroid administered. The receptor in the heart and the skeletal muscle was relatively sensitive to hormone injection while more than 4 times the amount of steroids was required to induce a similar effect in the thymus and the spleen. The duration of the period of depletion of the receptor in cytosols was also dose dependent and correlated to the biological potency of steroid administered. Replenishment took place earlier in the thymus and the spleen than in the heart and the skeletal muscle. Significantly lower binding affinity was observed in the replenished receptors. The administration of cycloheximide in a dose which inhibits more than 95% of3H-leucine incorporation did not influence either the depletion or the replenishment of the receptor induced by hormone injection. In conclusion, depletion and replenishment of the cytoplasmic glucocorticoid receptor appeared to be closely correlated to the physiological action of hormones.