Effects of bromocriptine on cell cycle distribution and cell morphology in cultured rat pituitary adenoma cells

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Abstract
The effects of bromocriptine a dopamine (DA) agonist, on cell cycle distribution and cell morphology have been studied in a clonal strain of rat pituitary adenoma cells (GH3) which produce and secrete spontaneously both prolactin (Prl) and growth hormone (GH). DNA flow cytometry showed that bromocriptine caused a dose-dependent delay in cell cycle traverse concomitantly with a reduction in cellular growth rate. The lowest concentration of bromocriptine (5 .times. 10-6 mol/l) significantly (P < 0.05) increased the relative number of cells in the S phase and reduced the proportion of cells in the G1 phase. At higher concentrations (1 .times. 10-5-5 .times. 10-5 mol/l) bromocriptine delayed cell cycle traverse through effects on cells in the S, G1 and G2 phases. These effects occurred already after 24 h of treatment. These results were supported by autoradiography of nuclear uptake of [3H]thymidine and by measurements of the number of cells arrested in metaphase after colcemide treatment (mitotic rate). Bromocriptine at 5 .times. 10-5 mol/l altered profoundly GH3 cell structure inducing cell clustering and typical changes in mitochondrial and nuclear ultrastructures. Since Prl and GH production is a characteristic of cells in G1 phase, the inhibitory effect of the lowest antiproliferative concentration of bromocriptine (5 .times. 10-6 mol/l) can only partly be explained in alterations in phase distribution. At the highest concentration of bromocriptine (5 .times. 10-5 mol/l) hormone production and cell division are also inhibited due to general toxic effects as reflected by the ultrastructural changes.

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