2-Bromo-alpha-ergocryptine causes degradation of prolactin in primary cultures of rat pituitary cells after chronic treatment.

Bromocriptine (2-bromo-a-ergocryptine) inhibited prolactin release when added to primary cultures of dispersed pituitary glands from male rats. The total amount of prolactin (intracellular plus extracellular) was reduced to less than 20% of control values after 6 days. The amount of intracellular prolactin was increased in treated cultures and the total amount of hormone was the same in control and treated cultures for the first 8 h that prolactin release was inhibited. After 4 days with bromocriptine, treated cultures did not contain more intracellular prolactin than control cultures. The rate of accumulation of total prolactin from 3 to 4 days after bromocriptine was added varied from 6-fold less than controls to no accumulation at all. The apparent rate of synthesis at this time, measured by the incorporation of [3H]leucine for 1 or 2 h, was only 1.4to 2.8-fold less in bromocriptine-treated cultures. After longer labeling periods, when the rate of accumulation of [3H]prolactin may increasingly reflect degradation as well as synthesis, the difference in the rate of accumulation became 6to 7-fold less than control. Stability of [3H]prolactin was measured by incubating the cells for 2 h with [3H]leucine and then adding 3 pg/ml of cycloheximide and 100-fold excess leucine. [3H]Prolactin was stable for 9 h in control cultures, but in bromocriptine-treated cultures there was a 40% decrease by 9 h. Therefore, at least some of the decrease in prolactin accumulation caused by bromocriptine results from degradation of the hormone.