Estrogenic activity of phenol red in rat anterior pituitary cells in culture

The estrogenic activity of phenol red, a pH indicator widely used in cell culture media, was studied in rat anterior pituitary cells. After 72 hours of incubation with 40 microM phenol red, a 40-50% increase in prolactin cell content and a 100% stimulation of luteinizing hormone-releasing hormone induced luteinizing hormone release was observed. Both effects could be completely reversed by simultaneous incubation with the antiestrogen LY156758. In the rat uterine [3H] estradiol binding assay, phenol red showed a significant displacement at concentrations above 10 microM while its concentration in the commonly used culture media is about 40 microM. From the present results, we conclude that phenol red acts as a weak estrogen in normal tissues and that its estrogenic activity should be taken into account in studies using estrogen-sensitive cell or tissue cultures.