Johansen P W, Haug E, Gautvik K M
Acta Endocrinol (Copenh). 1985 Oct;110(2):200-6. doi: 10.1530/acta.0.1100200.
Rat pituitary adenoma cells (GH3) that spontaneously synthesize and secrete both prolactin (Prl) and growth hormone (GH) were used in this study. Bromocriptine (5 X 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 X 10(-6) mol/l and 7 X 10(-6) mol/l, respectively. Maximum effect was obtained at 5 X 10(-5) mol/l of bromocriptine which after 24 h of treatment reduced the production of Prl and GH by approximately 70 and approximately 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 approximately 1 X 10(-5) mol/l and the maximum effect (greater than 50%) was observed at 5 X 10(-5) mol/l. All effects of bromocriptine were reversible upon cessation of treatment. The antiproliferative 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.
本研究使用了能自发合成和分泌催乳素（Prl）与生长激素（GH）的大鼠垂体腺瘤细胞（GH3）。多巴胺（DA）激动剂溴隐亭（5×10⁻⁵ mol/l）可使Prl和GH分泌迅速减少，处理15分钟后达到最大效应（约60%）。溴隐亭还以时间和剂量依赖的方式抑制Prl和GH的产生，其半数有效浓度（ED50）分别为4×10⁻⁶ mol/l和7×10⁻⁶ mol/l。在5×10⁻⁵ mol/l的溴隐亭作用下可获得最大效应，处理24小时后Prl和GH的产生分别减少约70%和约50%。处理9天后，Prl和GH的产生均减少超过95%。溴隐亭还降低了细胞生长速率。ED50约为1×10⁻⁵ mol/l，在5×10⁻⁵ mol/l时观察到最大效应（大于50%）。停止治疗后，溴隐亭的所有效应均可逆转。使用大鼠肝癌细胞系（MH1C1）和人上皮细胞系（HE）也观察到了溴隐亭的抗增殖作用，提示在高浓度药物作用下存在非受体介导的生长抑制。总之，溴隐亭对GH3细胞中Prl和GH分泌及产生的抑制作用发生在比其对细胞增殖作用更低的浓度。溴隐亭在体内对产生Prl和GH的腺瘤的药理作用可能是通过直接作用于垂体水平来解释的。
