Hormonal and morphologic effects of bromocriptine on normal rat pituitary and GH3 tumor cells.

Bromocriptine in concentrations up to 5 X 10(-4) mol/L was studied for any deleterious effects upon normal rat pituitary cells, as well as on the rat GH3 cell line. Normal rat pituitary glands were obtained by decapitation from 50-day-old female Wistar rats and dispersed with 0.25% trypsin. The cells (10(5) per plate) were then incubated in 60 by 15 mm plates (Falcon) that contained 3 ml of Dulbecco's modified Eagle's medium with 10% fetal calf serum. GH3 cells were plated in a similar fashion. Bromocriptine was added in concentrations of 5 X 10(-4) to 5 X 10(-9) mol/L, and aliquots of medium were obtained at 6, 24, and 48 hours for the determination of growth hormone and prolactin. Cell counts were performed at 24 and 48 hours. A significant reduction in concentrations of growth hormone and prolactin was observed with concentrations of bromocriptine of 5 X 10(-5) and 5 X 10(-4) mol/L at 24 and 48 hours (p less than 001). Although no significant changes in cell counts were observed in the normal rat pituitary cells, the GH3 cells showed complete disruption at 48 hours only in the plates that contained the highest concentrations of bromocriptine. Electron microscopy of normal rat cells and GH3 demonstrated selective cytotoxic effects only on the GH3 cells. In conclusion, bromocriptine has been demonstrated to have a direct effect on hormone release and on the morphologic characteristics of tumor cells but not normal pituitary cells.