G-PROTEINS IN NORMAL RAT PITUITARIES AND IN PROLACTIN-SECRETING RAT PITUITARY-TUMORS

It is still undetermined which GTP-binding (G) protein is involved in the regulation of prolactin (PRL) release and through which effector. This study shows that, when compared to normal pituitary tissue, the levels of alpha-o protein were very low in dopamine (DA)-resistant, PRL-secreting pituitary tumors 7315a and MtTWI5, while alpha-o mRNA was present in the two tumors. In the MtTWI5 tumor alpha-il, alpha-i2 and alpha-i3 levels were decreased while those of alpha-s42 and alpha-s47 were increased, and in the 7315a tumor alpha-i2, alpha-i3 and beta-levels were decreased and those of alpha-s47 increased. In an estrone-induced, DA-sensitive prolactinoma the levels of alpha-i3 were greatly reduced. DA was unable to inhibit basal PRL release by 7315a and MtTWI5 and basal cAMP accumulation by adenomatous and MtTWI5 cells. Vasoactive intestinal peptide (VIP) increased both cAMP accumulation and PRL release by all cell preparations which could be suppressed by DA with adenomatous and 7315a but not with MtTW15 cells. These and previously published results provide circumstantial evidence that alpha-o, alpha-il and alpha-i3 are all involved in the transduction of the DA inhibitory message while alpha-s47 transduces cAMP activating messages and alpha-s42 is responsible for the constitutive activation of L-type Ca2+ channels, adenylate cyclase and baseline PRL release.