Prolactin release from MtTW15 and 7315a pituitary tumors is refractory to TRH and VIP stimulation

We studied the in vitro responsiveness of prolactin-secreting MtTW15 and 7315a pituitary tumor cells to stimulation by selected secretagogues using a perifusion technique. Prolactin release by these cells was refractory to thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). In contrast, 50 mM K+, dibutyryl cAMP, theophylline, phospholipase A2 and phorbol myristate acetate all increased prolactin release from both tumor cell types. Phospholipase C increased prolactin release from 7315a but not from MtTW15 cells. TRH increased 32P incorporation into phosphatidylinositol in the 7315a but not in the MtTW15 tumor cells. Therefore, the refractoriness of these tumors to TRH and VIP may be at least partially due to a defect in the receptor or in the process that couples receptor binding and intracellular biochemical processes. In the MtTW15 tumor at least part of the defect may be related to phospholipid hydrolysis.