 Thyroliberin and dihydropyridines modulate prolactin gene expression through interacting pathways in GH3 cells; ; et al in Neuroendocrinology (1989), 50(6), 693-701 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 ... [more ▼] 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. [less ▲] Detailed reference viewed: 13 (0 ULg)Régulations de l'expression des gênes de la prolactine et de l'hormone de croissance dans des cellules hypophysaires en culture; ; Morin, Alexis  et alin Annales d'Endocrinologie (1986), 47(1), 22-7 The rat pituitary tumor derived cell lines of the "GH" family offer a fruitful model for studying the expressions of the prolactin (rPRL) and growth hormone (rGH) genes in basic and regulated states. In ... [more ▼] The rat pituitary tumor derived cell lines of the "GH" family offer a fruitful model for studying the expressions of the prolactin (rPRL) and growth hormone (rGH) genes in basic and regulated states. In order to assess the potential role of DNA methylation in the basic expressions of rPRL and rGH genes we have used different cell strains which produce either high level of rPRL (GH3B6 cells) or of rGH (GC cells) and minute amounts of both hormones (GH3CDL cells). The cleavage patterns generated by the methylation sensitive enzymes Hpa II and Msp I indicated an inverse correlation between the extent of gene methylation and the level of expression. However the use of 5-azacytidine which decreases DNA methylation suggested a variable importance of gene methylation in the respective control of rPRL and rGH genes depending on the cell lines. In an other hand we attempted to elucidate some of the mechanisms by which thyroliberin (TRH) enhances rPRL gene transcription in GH3B6 cells. Preliminary results indicated that the persistent occupancy of the TRH receptors was required to sustain at least for the first 5 hours the increased rate of rPRL gene transcription. In addition the possible relationship between the TRH-induced acute rPRL release and the stimulation of rPRL gene transcription was investigated. The results suggested that the activators of the C kinase-mediated pathway which are actually involved in the stimulation of the acute release were not sufficient alone for eliciting the maximum TRH response at the gene level. [less ▲] Detailed reference viewed: 22 (5 ULg) DNA methylation and expression of prolactin and growth hormone genes in a rat pituitary strain selected on steroid-depleted medium; Muller, Marc ; et alin MacLeod, R. M.; Thorner, M. O.; Scapagnini, U. (Eds.) Prolactin, basic and clinical correlates (1985) Detailed reference viewed: 12 (3 ULg)Inverse control of prolactin and growth hormone gene expression: effect of thyroliberin on transcription and RNA stabilization; ; et al in EMBO Journal (1983), 2(9), 1493-9 The hypothalamic tripeptide thyroliberin (TRH) regulates prolactin (PRL) and growth hormone (GH) synthesis inversely by modulating the levels of their specific mRNA. Changes in mRNA levels could involve ... [more ▼] The hypothalamic tripeptide thyroliberin (TRH) regulates prolactin (PRL) and growth hormone (GH) synthesis inversely by modulating the levels of their specific mRNA. Changes in mRNA levels could involve both transcriptional and posttranscriptional events. To examine further these possibilities, we have investigated the effect of TRH on the biosynthesis and degradation of PRL and GH RNA in a rat pituitary tumor cell line. Newly synthesized PRL and GH RNA sequences were quantified in nuclear and cytoplasmic fractions by hybridization of 3H-labelled RNA to immobilized plasmid DNA containing either PRL or GH cDNA sequences. Steady-state levels of specific RNA were estimated by RNA blot hybridization. The results indicate that TRH increases in a rapid but transient manner the transcription of the PRL gene, and suggest that it does not alter the processing and the transport to the cytoplasm. In contrast, after a lag-time, TRH seems to induce a long-lasting inhibition on GH, as well as on overall gene transcription. Furthermore, we observed an effect of TRH on mRNA stability. TRH significantly increases the half-life of PRL mRNA. Our results also support the hypothesis that TRH decreases the half-life of GH mRNA. Such post-transcriptional action of TRH amplifies and prolongs the regulations exerted at the transcriptional level. [less ▲] Detailed reference viewed: 5 (0 ULg) |
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