Lisuride, a dopamine agonist, inhibits DNA synthesis in the pituitary gland

We investigated the effects of lisuride, a potent dopaminergic agent, administered in vivo on the incorporation of 3H-thymidine into DNA and 3H-leucine into prolactin and its subsequent release by the rat anterior pituitary gland in vitro. The results demonstrated that daily injection of 100 micrograms of lisuride for 7 days significantly (p less than 0.05) diminished (about 35%) the incorporation of 3H-thymidine into DNA and reduced the stimulation of DNA synthesis produced by estrogens. The incorporation of 3H-leucine into prolactin was markedly inhibited by the administration of lisuride, and also significantly (p less than 0.05) reduced the stimulation of prolactin secretion produced by estrogens. In pituitary glands enlarged by the chronic administration of estrogens, lisuride treatment significantly (p less than 0.05) reduced the weight (26%), the content of DNA (35%) and the incorporation of 3H-thymidine (40%). The inhibitory effect of lisuride on DNA synthesis was present as early as 20 h after a single injection of the drug (about 27%). The same treatment with lisuride significantly (p less than 0.05) reduced the incorporation of 3H-leucine into prolactin. The results of these experiments are compatible with the concept of a relationship between prolactin release and DNA synthesis in the pituitary gland. They also suggest that lisuride, as with bromocriptine, may exert its antiproliferative effects on prolactin-secreting adenomas by decreasing their synthesis of DNA.