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Glucocorticoid Hormones Negatively Regulate Nerve Growth Factor Expression In Vivo and in Cultured Rat Fibroblasts
Author(s) -
Lindholm Dan,
Hengerer Bastian,
Heumann Rolf,
Carroll Patrick,
Thoenen Hans
Publication year - 1990
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1990.tb00471.x
Subject(s) - nerve growth factor , medicine , endocrinology , glucocorticoid , sciatic nerve , biology , reporter gene , dexamethasone , chloramphenicol acetyltransferase , gene expression , gene , biochemistry , receptor
Sciatic nerve transection leads to an up‐regulation of nerve growth factor (NGF) production in non‐neuronal cells surrounding the axons. The lesion‐mediated increase in NGF‐mRNA levels in the nerve can be blocked by pretreating the animals with the synthetic glucocorticoid dexamethasone. Dexamethasone also reduces NGF‐mRNA levels in cultured sciatic fibroblasts stimulated with fetal calf serum or interleukin‐1. In order to study at which level glucocorticoids down‐regulate NGF expression, sciatic fibroblasts where transfected with a construct in which a reporter gene (chloramphenicol acetyltransferase) is expressed under the control of the NGF promotor. The results demonstrated that dexamethasone effectively represses NGF gene transcription. Deletion experiments showed that a 162 nucleotide promotor region mediates the glucocorticoid hormone suppression of NGF expression. The negative regulation of NGF synthesis by glucocorticoids is a factor to be considered in the treatment of patients with peripheral nerve lesions.