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Thyroid Hormone‐Regulated Expression of RC3/Neurogranin in the Immortalized Hypothalamic Cell Line GT1‐7
Author(s) -
Morte Beatriz,
Iñiguez Miguel Angel,
Lorenzo Petra Isabel,
Bernal Juan
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.69030902.x
Subject(s) - neurogranin , biology , transactivation , medicine , retinoic acid , nuclear receptor , endocrinology , receptor , thyroid hormone receptor , signal transduction , cell culture , microbiology and biotechnology , gene expression , hormone , protein kinase c , transcription factor , gene , biochemistry , genetics
The calmodulin‐binding, protein kinase C substrate RC3/neurogranin is the product of a neuron‐specific gene expressed in the forebrain that is under specific regional and temporal control by thyroid hormone (3,5,3′‐triiodothyronine, T 3 ). In vivo, some neuronal populations are sensitive and others are insensitive to T 3 . The goal of this study was to identify neuronal cell cultures that express RC3/neurogranin, to check whether they are sensitive to T 3 , and to examine the mechanism of regulation. We found that RC3 is induced by T 3 in the hypothalamic cell line GT1‐7 at the transcriptional level. The half‐life of the mature mRNA was 20 h and was not affected by the hormone. Addition of T 3 to the cell culture induces neurogranin mRNA after 6 h in the absence of new protein synthesis. These results suggest a direct transcriptional effect of T 3 mediated through nuclear receptors. Indeed, GT1‐7 cells express functional T 3 receptors, as shown by northern blotting, nuclear T 3 ‐binding assays, and transactivation of reporter genes. The role of retinoic acid and glucocorticoids on RC3 expression was also evaluated, because we have previously noted the presence of consensus response elements for these hormones in the RC3 upstream promoter region. In contrast to T 3 , neither retinoic acid nor dexamethasone influences neurogranin expression despite the presence of respective functional receptors.