Transient inhibition of cell proliferation in rat glioma monolayer cultures by cortisol.

Abstract

The effect of 3 muM cortisol on cell proliferation in rat glioma (strain C6) monolayer cultures was investigated. Cell density measurements showed that cortisol-treated C6 cells continued to proliferate at maximum log phase rates for 1 to 2 days. Then cell proliferation ceased as growth in control cultures continued into stationary phase. A 2-day period of growth inhibition followed during which cell densities were 30 to 50% lower relative to controls. Growth resumed subsequently, and final cell densities were similar to those of controls. The presence of epicortisol (the biologically inactive isomer of cortisol) in the culture medium did not alter the rate of log phase growth relative to controls. During the initial period of continued growth after exposure to cortisol, the pH of the medium decreased at the same rate in control and treated cultures. During the growth-inhibitory period, erythrosin B dye was excluded equally well (greater than 94%) by control and treated cells, and no morphological differences were detected by phase contrast microscopy. When the culture medium was replaced daily, the control cells at elevated densities continued to proliferate at a reduced rate. In cortisol-treated cultures, the period of growth inhibition commenced 3 days after the cells were exposed initially to cortisol. A 2-day period of growth inhibition followed during which the pH of the 1-day-old media from both control and treated cultures decreased from 7.4 to 6.9. Growth resumed subsequently in the treated cultures to produce elevated cell densities similar to those of controls. These results demonstrate that cortisol at concentrations considered chemotherapeutic in vivo exerts a transient inhibitory effect on C6 glioma cell proliferation.