Effects of bromocriptine on hormone production and cell growth in cultured rat pituitary cells

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Abstract
Rat pituitary adenoma cells (GH3) that spontaneously synthesize and secrete both prolactin (Prl) and growth hormone (GH) were used in this study. Bromocriptine (5 × 10−5 mol/l), a dopamine (DA) agonist, induced a rapid reduction in Prl and GH secretion with maximum effect (approximately 60%) after 15 min of treatment. Bromocriptine also inhibited Prl and GH production in a time- and dose-dependent manner with ED50 at 4 × 10−6 mol/l and 7 × 10−6 mol/l, respectively. Maximum effect was obtained at 5 × 10−5 mol/l of bromocriptine which after 24 h of treatment reduced the production of Prl and GH by ∼ 70 and ∼ 50%, respectively. After 9 days of treatment both Prl and GH production was reduced by more than 95%. Bromocriptine also reduced cellular growth rate. The ED50 was ∼ 1 × 10−5 mol/l and the maximum effect (> 50%) was observed at 5 × 10−5 mol/l. All effects of bromocriptine were reversible upon cessation of treatment. The anti-proliferative effect of bromocriptine was also observed using a rat hepatoma cell line (MH1C1) and a human epithelial cell line (HE), suggesting a non-receptor mediated growth inhibition at high concentrations of the drug. In conclusion, the inhibitory effect of bromocriptine on secretion and production of both Prl and GH in GH3 cells occurs at a lower concentration than its effect on cell proliferation. The pharmacological effects of bromocriptine in vivo on Prl and GH producing adenomas may be explained by an action directly at the pituitary level.