Vinblastine and nocodazole inhibit basal and thyrotropin-releasing hormone-stimulated prolactin secretion in GH₃ cells

Abstract

To investigate the efficacy of vinblastine as a possible therapeutic agent in prolactinomas, we have examined the effects of vinblastine on GH₃ cell function. The effects of vinblastine were compared to another anti-microtubule drug, nocodazole. At 24 h, prolactin (PRL) secretion was 737±63 ng/ml in control cells. In cells treated with 0.1, 1 and 10μm nocodazole for 24 h, PRL secretion was reduced to 200±30 ng/ml. After a 24 h incubation with the drugs, cells were washed with drug-free medium and challenged with 100nm TRH for 10 min. TRH-stimulated PRL secretion was 35±7 ng/ml in control cells, 14±0.5 ng/ml in vinblastine-treated cells and 8.8±0.1 ng/ml in nocodazole-treated cells. [³H]TRH binding to GH₃ cell membrane was inhibited by about 15% by vinblastine and nocodazole. In vinblastine and nocodazole treated cells, polymerized tubulin levels decreased by 46 and 55%, respectively. These observations that vinblastine suppresses PRL secretion by GH₃ cells suggest that this drug might be useful as a therapeutic agent for prolactinomas.