title: Transcriptional induction of rat mineralocorticoid receptor gene in neurones by corticosteroids.
abstract: We investigated the mechanisms by which corticosteroids regulate the expression of the mineralocorticoid receptor (MR) in neurones. Aldosterone and dexamethasone produced a dose-dependent increase of MR and mRNA levels in cultured primary hippocampal neurones. Transient transfection of neuroblastoma cells showed that corticosteroids directly activate the rat MR promoter, indicating that the steroid-induced increase in the MR mRNA concentration is at least partially transcriptional. Progressive 5' deletions of the MR promoter sequence revealed that the promoter induction cannot be assigned to a single element. An oligonucleotide comprising a consensus half-glucocorticoid responsive element located at -319 bp in the MR promoter stimulated the corticosteroid-induced activation of the heterologous promoter. Cloning three of these enhancers in tandem greatly potentiated the responses to glucocorticoids and mineralocorticoids, suggesting that although this element is a weak enhancer it can, in combination with other enhancer elements, induce MR gene expression by both types of corticosteroid receptors.
authors.affiliation: Department of Neuroendocrinology, Max-Planck-Institute of Psychiatry, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Castrén
authors.forename: T
authors.initials: T
authors.lastname: Trapp
authors.forename: B
authors.initials: B
authors.lastname: Berninger
authors.forename: E
authors.initials: E
authors.lastname: Castrén
authors.forename: F
authors.initials: F
authors.lastname: Holsboer
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D016384:Consensus Sequence; D003345:Corticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004742:Enhancer Elements, Genetic; D017930:Genes, Reporter; D006624:Hippocampus / Q000166:cytology; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis / Q000235:genetics*; D017384:Sequence Deletion; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000305:Adrenal Cortex Hormones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D003907:Dexamethasone; D003345:Corticosterone