Effect of Cabergoline, a Dopamine Agonist, on Estrogen-Induced Rat Pituitary Tumors

In Vitro Culture Studies

抄録

Cabergoline (CG) is a dopamine agonist that inhibits secretion of prolactin (PRL) and growth hormone. The purpose of this study was to investigate the PRL-lowering effect and antitumor effect of CG on estradiol-induced rat pituitary tumors in vitro and to elucidate these mechanisms. We compared the effects of CG with those of bromocriptine (BC) in terms of the inhibition of hormone secretion as well as antitumor effects on rat pituitary tumors. Primary cultures of dissociated pituitary tumor cells were used in these studies. A significant inhibition of prolactin (PRL) secretion was observed for both drugs within 12h after treatment, and the inhibitory effects of CG and BC were antagonized by sulpiride or haloperidol. Inhibitory effect on PRL secretion after 12-h BC or CG pretreatment was more pronounced with CG than BC treatment at all time points. PRL secretion in group pretreated with CG was significantly suppressed at 72h when compared to that of vehicle. Inhibition of de novo PRL synthesis was better demonstrated in the CG group. These findings suggest that CG has a higher affinity for the D₂ receptor of pituitary cells as compared to BC and may preferentially inhibit PRL secretion rather than PRL production. An antitumor effect of CG has been confirmed at a lower dosage than that of BC.