Dexamethasone blocks antioestrogen- and oxidant-induced death of pituitary tumour cells

C. J. Newton, D. Bilko, S. Pappa, Stephen Atkin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The oestrogen receptor is fundamental to the growth and survival of the rat pituitary tumour cell line, GH3. Our previous studies have shown that antioestrogens such as RU 58668 and ZM 182780 will reduce the rate of cell division and also induce cell death. Death of these cells in response to antioestrogen treatment appears to be due to a heightened sensitivity to reactive oxygen species (ROS). As part of a study to determine the cross-talk between steroid receptor systems in these cells, we have observed that the glucocorticoid, dexamethasone (Dex), inhibits antioestrogen-induced cell death. Cell death induced by H2O2 is enhanced by ZM 182780 and this effect is also blocked by Dex. As apoptotic cell death in a number of systems involves an early loss of mitochondrial membrane potential (Δψm), we have performed detailed studies on the time-course of Δψm loss in relation to the loss in cell membrane function. These studies have indicated that a loss of Δψm parallels a loss of cell membrane function - this is more characteristic of necrosis than of apoptosis. From microscopic observations of these cells in response to H2O2, it has been noted that early cell membrane blebbing, induced by H2O2, is blocked in the presence of ZM 182780. Cell membrane blebbing can precede necrosis as well as apoptosis and it is thought to involve cytoskeletal changes, for which localised glycolytic reactions provide ATP. These observations, together with those showing that removal of glucose, but not inhibition of mitochondrial function, enhances ROS-induced cell death, prompted studies on the glycolytic pathway. As a strong candidate mechanism, it would appear that, via an effect on one of the rate-limiting glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase, Dex is able to overcome the antioestrogen-enhanced loss of glycolytic function following exposure of cells to ROS. This report contributes to the growing body of evidence showing that glucocorticoids provide a survival advantage to both normal and tumour cell types.

Original languageEnglish
Pages (from-to)249-261
Number of pages13
JournalJournal of Endocrinology
Volume169
Issue number2
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Estrogen Receptor Modulators
Pituitary Neoplasms
Oxidants
Dexamethasone
Cell Death
Cell Membrane
Reactive Oxygen Species
Blister
Glucocorticoids
Necrosis
Apoptosis
Glyceraldehyde-3-Phosphate Dehydrogenases
Mitochondrial Membrane Potential
Steroid Receptors
Tumor Cell Line
Estrogen Receptors
Cell Division
Adenosine Triphosphate
Glucose
Enzymes

ASJC Scopus subject areas

  • Endocrinology

Cite this

Dexamethasone blocks antioestrogen- and oxidant-induced death of pituitary tumour cells. / Newton, C. J.; Bilko, D.; Pappa, S.; Atkin, Stephen.

In: Journal of Endocrinology, Vol. 169, No. 2, 2001, p. 249-261.

Research output: Contribution to journalArticle

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