Since the
gonadotropin-releasing hormone-associated peptide (GAP) has been reported to be capable of inhibiting
prolactin release from normal lactotrophs, with the present study we have examined the in vitro effects of GAP on
prolactin release in an
estrone-induced,
dopamine-sensitive rat
pituitary adenoma and two malignant, transplantable and
dopamine-resistant rat
pituitary tumors, 7315a and MtTW15. Enzymatically dispersed cells obtained from the three types of
tumor were cultured in multiwell dishes for 4 days. On the fifth day, the cells were exposed for 4 h to human GAP 1-56 or to the analog GAP 42-56 or to rat GAP 1-53, at various concentrations. In some experiments, the effect of a pretreatment of the cells for 16 h with
pertussis toxin before exposure to human GAP was also evaluated. In the three tissues, rat GAP was able to inhibit
prolactin release in a dose-dependent manner. Human GAP 1-56 and GAP 42-56 were able to inhibit
prolactin release in a dose-dependent manner in all cells except those of the MtTW15
tumor. Furthermore, in adenomatous cells, the inhibitory effects of these
peptides were suppressed by pretreatment of the cells with
pertussis toxin. These findings indicate that GAP is capable of inhibiting
prolactin release even in
dopamine-resistant
pituitary tumors. This inhibition is exerted through a
pertussis toxin-sensitive
G-protein-dependent signaling mechanism in adenomatous cells.