Glucocorticoid binding proteins in human acute lymphoblastic leukemic blast cells

Marc E Lippman, R. H. Halterman, B. G. Leventhal, S. Perry, E. B. Thompson

Research output: Contribution to journalArticle

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Abstract

The first known step in steroid hormone action is the association of the steroid with specific cytoplasmic steroid binding proteins (SBP). Using a competitive binding assay the authors detected, quantified, and partially characterized such a SBP in cytosol from glucocorticoid sensitive human lymphoblastic leukemic blasts. The affinity of steroids for the SBP was directly related to their known killing potency. For example, steroids without glucocorticoid effect such as androstenedione, etiocholanolone, and tetrahydrocortisol were unable to displace radiolabeled dexamethasone from the SBP in the binding reaction. The dose response curve for in vitro inhibition of [ 3H] thymidine uptake in leukemic blasts correlated closely with the binding affinity of glucocorticoids to the SBP, providing additional support for an essential physiologic role for SBP in steroid action. SBP activity was either greatly diminished or absent in glucocorticoid resistant cells. 6 patients who intially had SBP in their blasts and were responsive to combinations of drugs including glucocorticoids no longer had SBP activity detectable at a time when they no longer responded to combinations of drugs including glucocorticoids. In vitro [ 3H] thymidine uptake was not inhibited by steroids in leukemic blast cells lacking SBP activity. Other patients who had received some antileukemic therapy including glucocorticoids and who still had SBP in their leukemic blasts, were still responsive to drug combinations that included glucocorticoids. This appears to be the first study demonstrating glucocorticoid receptors in a human tissue.

Original languageEnglish
Pages (from-to)1715-1725
Number of pages11
JournalJournal of Clinical Investigation
Volume52
Issue number7
StatePublished - Dec 1 1973
Externally publishedYes

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Glucocorticoids
Carrier Proteins
Steroids
Drug Combinations
Thymidine
Tetrahydrocortisol
Etiocholanolone
Competitive Binding
Androstenedione
Glucocorticoid Receptors
Protein Binding
Cytosol

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lippman, M. E., Halterman, R. H., Leventhal, B. G., Perry, S., & Thompson, E. B. (1973). Glucocorticoid binding proteins in human acute lymphoblastic leukemic blast cells. Journal of Clinical Investigation, 52(7), 1715-1725.

Glucocorticoid binding proteins in human acute lymphoblastic leukemic blast cells. / Lippman, Marc E; Halterman, R. H.; Leventhal, B. G.; Perry, S.; Thompson, E. B.

In: Journal of Clinical Investigation, Vol. 52, No. 7, 01.12.1973, p. 1715-1725.

Research output: Contribution to journalArticle

Lippman, ME, Halterman, RH, Leventhal, BG, Perry, S & Thompson, EB 1973, 'Glucocorticoid binding proteins in human acute lymphoblastic leukemic blast cells', Journal of Clinical Investigation, vol. 52, no. 7, pp. 1715-1725.
Lippman ME, Halterman RH, Leventhal BG, Perry S, Thompson EB. Glucocorticoid binding proteins in human acute lymphoblastic leukemic blast cells. Journal of Clinical Investigation. 1973 Dec 1;52(7):1715-1725.
Lippman, Marc E ; Halterman, R. H. ; Leventhal, B. G. ; Perry, S. ; Thompson, E. B. / Glucocorticoid binding proteins in human acute lymphoblastic leukemic blast cells. In: Journal of Clinical Investigation. 1973 ; Vol. 52, No. 7. pp. 1715-1725.
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