The Role of Cytoplasmic Glucocorticoid Receptors in the Cytolysis of Human Lymphoblastoid Cells by Methylprednisolone

Waddell, A W; Bird, C. C.; Currie, A. R.

doi:10.1042/bst0050719a

Cited by 7 publications

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“…Effects of 1 mM-prednisolone and -methylprednisolone on uridine uptake into BLA1 cells Samples (2ml) of BLA1 cells (106/ml) in modified Eagle's medium (Gibco-Biocult, Paisley, Scotland, U.K.) buffered with NaHCO3 and supplemented with 20O (v/v) foetal calf serum (Gibco-Biocult) were pulsed for 20min with [3H]uridine (1 pCi/ml) after preincubation with methylprednisolone (1 mM), prednisolone (1 mM) or 0.9°. (Waddell et al, 1976(Waddell et al, , 1977. Since methylprednisolone is more effective than prednisolone in producing both long-term (i.e.…”

Section: Resultsmentioning

confidence: 99%

“…We have examined the effects of glucocorticoids on human lymphoblastoid cells in culture as part of a study ofcell death. Methylprednisolone at about 1 mm causes the lysis of human lymphoblastoid cells (Bird et al, 1975) and inhibits the uptake of uridine and thymidine into these cells (Waddell et al, 1976(Waddell et al, ,1977. Cytolysis is a long-term effect, requiring the continuous presence of glucocorticoid for up to 48h for maximal effect, whereas the inhibition of uptake of uridine and thymidine is apparently instantaneous.…”

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A comparison of the effects of prednisolone and methylprednisolone on human lymphoblastoid cells

Waddell¹,

Currie²

1977

Biochemical Journal

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

A comparison of the effects of prednisolone and methylprednisolone on human lymphoblastoid cells

Waddell¹,

Currie²

1977

Biochemical Journal

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“…However, studies by others involving a wider spectrum of haematological malignancy have been unable to confirm that a close correlation necessarily exists between levels of glucocorticoid binding and the in-vivo and invitro responsiveness of leukaemic cells to glucocorticoid therapy (Crabtree, Smith & Munck 1978, Iacobelli et al 1978, Simonsson, Terenius & Nilsson 1978b, Homo et al 1980, Kontula et al 1980). Similar difficulties have been encountered with in-vitro studies of a large series of human lymphoid cell lines derived from various haematological malignancies , Waddell, Bird & Currie 1977, Robertson et al 1978, Barrett et al 1981, Burrow et al 1981. In the latter studies, despite high levels of glucocorticoid binding, massive concentrations of hormone were required to induce in-vitro cytolethal responses in nearly every cell line investigated.…”

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confidence: 87%

Glucocorticoid binding and cytolethal responsiveness of hairy-cell and chronic lymphocytic leukaemia

Barrett

Panesar

Burrow

et al. 2008

Clinical &Amp; Laboratory Haematology

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Summary The glucocorticoid binding properties and cytolethal responsiveness of leukaemic cells were studied in vitro in seven patients with hairy‐cell leukaemia (HCL) and five with chronic lymphocytic leukaemia (CLL). Substantial levels of glucocorticoid binding were detected both in whole cell and cytosol preparations from all patients although the level of binding by HCL cells always exceeded that of CLL cells (P>0.05). In both leukaemic cell types the uptake and binding of prednisolone in vitro was significantly greater than that of dexamethasone (P>0.05). CLL cells showed a variable dose‐related cytolethal response to methylprednisolone sodium succinate (MPSS) treatment in vitro although cytolytic effects were not marked in the usual pharmacological dose range (10‐5‐106m). Treatment of CLL patients with conventional doses of prednisone for extended periods or high intravenous infusions of MPSS over shorter periods had no consistent effect on the in‐vitro level of steroid binding or the cytolethal responsiveness of CLL cells to glucocorticoid treatment. Although HCL cells proved highly resistant to the cytolethal effects of MPSS in vitro, the substantial binding of glucocorticoids by leukaemic cells from all HCL patients indicates the potential value of steroid therapy in this disease should be explored further.

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Glucocorticoid receptors and glucocorticoid sensitivity of human leukemic cells

Kontula

Andersson

Paavonen

et al. 1980

Intl Journal of Cancer

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We have established optimal conditions for the measurement of glucocorticoid receptors (GR) in human white cells using a whole-cell binding assay with [3H]dexamethasone as the ligand, and the subsequent determination of the GR content in normal human lymphocytes and in leukemic cells of patients with various forms of acute and chronic leukemia. A number of leukemia cell lines in continuous culture were also subjected to the GR assay, and the results were correlated with the sensitivity of these cell lines to glucocorticoid steroids in vitro. The GR content of normal human lymphocytes amounted to 4,850 +/- 1,340 (mean +/- SD) receptors/cell. The mean equilibrium dissociation constant (KD) of the interaction of [3H]dexamethasone with the GR was 1.2 x 10(-8) M. Steroidal compounds with a known glucocorticoid potency effectively competed for the binding, whereas steroids devoid of glucocorticoid activity (e.g. estradiol-17 beta and testosterone) were ineffective. The GR content of the blast cells obtained from eight patients suffering from acute leukemia and four patients with a blast crisis of chronic myelocytic leukemia was found to be highly variable (3,230-29,900 receptors/cell), while the lymphocytes of six patients with chronic lymphatic leukemia contained a rather stable GR content (2,930-5,120 receptors/cell), which was comparable with that of normal lymphocytes. GR was identified in all the 12 malignant continuous white cell lines studied. Large cells contained more GR than the smaller ones. There was no apparent correlation between the GR concentration and the sensitivity of the cells in vitro to glucocorticoids as judged by [3H]thymidine incorporation studies. Distribution of the surface markers in the leukemic cell lines did not relate to the GR concentration. We conclude that the presence of GR is probably a universal feature of the leukemic cells, and, from a clinical standpoint, probably does not alone imply steroid responsiveness.

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The Role of Cytoplasmic Glucocorticoid Receptors in the Cytolysis of Human Lymphoblastoid Cells by Methylprednisolone

Cited by 7 publications

References 0 publications

A comparison of the effects of prednisolone and methylprednisolone on human lymphoblastoid cells

A comparison of the effects of prednisolone and methylprednisolone on human lymphoblastoid cells

Glucocorticoid binding and cytolethal responsiveness of hairy-cell and chronic lymphocytic leukaemia

Glucocorticoid receptors and glucocorticoid sensitivity of human leukemic cells

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