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 MtTW15, while alpha o mRNA was present in the two tumors. In the MtTW15 tumor alpha i1, 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 MtTW15 and basal cAMP accumulation by adenomatous and MtTW15 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 i1 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.
Bouvier
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C
Research Unit on Reproductive and Developmental Biology, Ste-Justine Hospital, Montreal, Quebec, Canada.
Forget
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H
Lagacé
G
G
Drews
R
R
Sinnett
D
D
Labuda
D
D
Collu
R
R
D000236:Adenoma / Q000139:chemically induced / Q000737:chemistry*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis / Q000502:physiology; D003864:Depression, Chemical; D004298:Dopamine / Q000494:pharmacology; D004351:Drug Resistance; D004970:Estrone / Q000633:toxicity; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification*; D013006:Growth Hormone / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000737:chemistry*; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000737:chemistry* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D015175:Prolactinoma / Q000737:chemistry* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D051381:Rats; D011915:Rats, Inbred BUF; D011916:Rats, Inbred F344; D011920:Rats, Inbred WF; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011954:Receptors, Dopamine; D004970:Estrone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D004298:Dopamine