Inverse control of prolactin and growth hormone gene expression: effect of thyroliberin on transcription and RNA stabilization.

Abstract

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.

Immunocytochemical Evidence for in vivo Internalization of Thyroliberin into Rat Pituitary Target Cells

“…However, this is consistent with previous results obtained for TRH in GHj cells using both autoradiography and cell fractionation [3,12,17,18]. Moreover, we previ ously reported a nuclear localization of gonadoliberin [23], substance P [22], vasoactive intestinal peptide [21], cortico tropin-releasing factor [25], So, TRH seems to be internalized in its pituitary target cells as previously suggested for GHj cells [3,12].…”

Effect of dimethyl sulfoxide on human carcinoma cells, inhibition of plasminogen activator synthesis, change in cell morphology, and alteration of response to cholera toxin.

“…Results obtained in a number of tumor systems, in addition to our previous observations with HEp-3 cells, indicate (3,20,22,26).…”

“…Tissue culture dishes were obtained from Becton Dickinson Labware, Oxnard, Calif., and tissue culture plates (model FB [16][17][18][19][20][21][22][23][24] were obtained from Linbro Scientific, Hamden, Conn.…”

Hypophyseal cells model systems: the ?GH? rat tumor-derived cell lines as a tool for the study of gene expression

“…The TRH-induced stimulation of PRL mRNA is now classical (Laverriere et al, 1983;Laverriere et al, 1988;Laverriere et al, 1991;Richard et al, 1991).This essentially originates in a rapid stimulation of the PRL gene transcription. The coupling between TRH receptors to such effect was established in term of dose-dependency (EC 50 ---0.5-1nM, E max = 10 nM) and kinetics (Laverriere et al, 1983).…”

“…The results presented were chosen to illustrate: 1) the differential responsiveness of the above mentioned genes in response to external signals known to regulate the secretion of PRL and GH hormones; 2) examples of a pharmacological approach of intracellular mechanisms involved in the regulation of gene expression by external signals (Gourdji et al, 1982;Laverriere et al, 1983;Weisman et al, 1987;Laverriere et al, 1988;Laverriere et al, 1989;Gourdji et al, 1991;Laverriere et al, 1991;Richard et al, 1991).…”