Glucocorticoid Hormones Negatively Regulate Nerve Growth Factor Expression In Vivo and in Cultured Rat Fibroblasts.
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.
Lindholm
Dan
D
Department of Neurochemistry, Max-Planck-Institute for Psychiatry, Am Klopferspitz 18 A, D-8033, Martinsried/Munich, FRG.
Hengerer
Bastian
B
Heumann
Rolf
R
Carroll
Patrick
P
Thoenen
Hans
H