Thyroliberin and dihydropyridines modulate prolactin gene expression through interacting pathways in GH3 cells.
The stimulation of PRL gene transcription by TRH involves the two branches of the phosphatidyl inositol pathway as shown by pharmacological mobilization of intracellular Ca2+ stores and activation of protein kinase C. However, TRH receptor occupancy also results in the activation of voltage-dependent Ca2+ channels. Thus, we attempted to determine whether a specific class of voltage-dependent Ca2+ channels, the dihydropyridine (DHP)-sensitive Ca2+ channels, might also be involved in the transcriptional action of TRH. This was studied in rat pituitary tumor GH3B6 cells by runoff assay and measurement of mRNA levels, using two DHPs, BAY K8644 which increases and PN 200-110 which decreases the influx of Ca2+. We show that the PRL mRNA levels and the rate of PRL gene transcription were stimulated by BAY K8644 and inhibited by PN 200-110 in a dose-dependent manner indicating that DHP-sensitive Ca2+ channels can control the expression of the PRL gene. Furthermore, PN 200-110 abolished the BAY K8644-induced stimulations. By contrast, the stimulations of the PRL gene expression induced by TRH or by the phorbol ester TPA were not abolished by the calcium channel antagonist PN 200-110 whereas treatments combining TRH or TPA with BAY K8644 revealed the absence of any additive effect. Altogether these observations suggest that TRH, and TPA, might activate pathway(s) interacting with those triggered by the Ca2+ channel agonist for regulating PRL gene transcription but they do not support the hypothesis of a necessary implication of DHP-sensitive calcium channels in the regulation of PRL gene transcription by TRH.
Laverrière
J N
JN
Unité Associée 1115, Centre National de la Recherche Scientifique, Collége de France, Paris.
Richard
J L
JL
Buisson
N
N
Martial
J A
JA
Tixier-Vidal
A
A
Gourdji
D
D
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D017275:Isradipine; D007700:Kinetics; D010069:Oxadiazoles / Q000494:pharmacology; D010911:Pituitary Neoplasms; D011388:Prolactin / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D010069:Oxadiazoles; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011388:Prolactin; D013755:Tetradecanoylphorbol Acetate; D017275:Isradipine