Glucocorticoid Hormones Negatively Regulate Nerve Growth Factor Expression In Vivo and in Cultured Rat Fibroblasts

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Abstract
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 levels 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 NGG promoter. The results demonstrated that dexamethasone effectively represses NGF gene transcriptpion. Deletion experiments showed that a 162 nucleotide promoter region mediates the glucocorticoid hormone suppression of NGF expression. The negative regulation of NGF synthesis by glucocotricoids is a factor to be considered in the treatment of patients with peripheral nerve lesions.