Activation of thyrotropin-releasing hormone gene expression in cultured fetal diencephalic neurons by differentiating agents

Endocrinology
T O BruhnI M Jackson

Abstract

The present studies were undertaken to investigate the effect of 5-bromo-2'-deoxyuridine (BrdU; 50 microM) or forskolin/3-isobutyl-1-methylxanthine (F/I; 10/500 microM) on TRH gene expression in cultured fetal diencephalic cells. BrdU as well as drugs such as F/I that raise intracellular cAMP levels had been previously termed differentiating agents because they cause morphological and functional differentiation of IMR-32 neuroblastoma cells. We postulated that neurons of fetal diencephalons may remain relatively undifferentiated in vitro and that this might be the reason for low or undetectable TRH production. We hypothesized that treatment with differentiating agents might increase neuropeptide expression. Both BrdU and F/I dramatically (P < 0.01) raised intracellular TRH and pro-TRH messenger RNA concentrations in cultured diencephalic neurons. Although a short BrdU exposure during the first 4 days of culture was sufficient to irreversibly change TRH neurons and to cause maintenance of high TRH levels after withdrawal of the drug, F/I had to be present continuously throughout the observation period of 16 days to significantly elevate TRH expression. This suggests that BrdU and F/I act at different intracellular sites to activ...Continue Reading

Citations

Sep 15, 2001·Brain Research. Developmental Brain Research·L Pérez-MartínezP Joseph-Bravo
Dec 1, 1999·Endocrinology·E A NillniO H Pescovitz
Apr 2, 2004·Revista brasileira de psiquiatria : orgão oficial da Associação Brasileira de Psiquiatria, Asociación Psiquiátrica de la América Latina·Saint-Clair Bahls, Gisah Amaral de Carvalho
Sep 24, 2021·Scientific Reports·Alexander G StepchenkoElizaveta V Pankratova

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