Specificity and Sensitivity of Cortisol-Induced Changes in Alpha Aminoisobutyric Acid Transport in Human Leukemic Small Lymphocytes and Leukemic Myeloblasts

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Abstract

We have examined the in vitro effect of glucocorticoid and nonglucocorticoid steroids on the transport of [3-14C]alpha aminoisobutyric acid (AIB) in lymphocytes from patients with chronic lymphocytic leukemia (CLL), and myeloblasts from patients with acute granulocytic leukemia (AGL). AIB uptake by CLL lymphocytes was markedly inhibited at 1.0 μM (52±2.1%) and slightly inhibited at 0.1 μM (17±3.0%) cortisol. A similar degree of inhibition developed at 50-fold lower concentrations of dexamethasone, indicating that the effect of these steroids on AIB accumulation parallels their glucocorticoid activity in vivo. In contrast, minimal or no inhibition was observed with steroids devoid of glucocorticoid activity (progesterone, testosterone, cortisone). 11-deoxycortisol, a nonglucocorticoid known to impede the binding of cortisol to cellular receptors in animal lymphocytes, failed to inhibit AIB uptake by CLL lymphocytes appreciably, but reduced the effect of cortisol to a statistically significant degree. Hence, cortisol-induced inhibition of AIB transport in CLL lymphocytes is related to its glucocorticoid activity and appears to require initial interaction with glucocorticoid-specific cellular receptors.

Authors

Patrick A. Frengley, Marshall A. Lichtman, William A. Peck