ESTROGEN DIFFERENTIALLY REGULATES ESTROGEN AND NERVE GROWTH-FACTOR RECEPTOR MESSENGER-RNAS IN ADULT SENSORY NEURONS

We have previously shown that neurons in the basal forebrain colocaliz e the neurotrophin receptor p75(NGFR) and estrogen receptors. The pres ent study was designed to examine(l) if neural neurotrophin targets re spond to estrogen as a general phenotypic feature and (2) if NGF recep tor mRNAs are regulated by estrogen, using a prototypical target of NG F, the dorsal root ganglion (DRG) (sensory) neuron. We demonstrate, fo r the first time, the presence of estrogen receptor mRNA and protein ( binding sites) in adult female rat DRG. Moreover, estrogen receptor mR NA expression, while present in DRG neurons from both the ovariectomiz ed (OVX; estrogen deficient) and intact female rat, was downregulated, as in the adult CNS, during proestrus (high estrogen levels) and in O VX animals replaced with proestrus levels of estrogen, as compared to OVX controls. In contrast, although the mRNAs for the NGF receptors p7 5(NGFR) and trkA were also expressed in DRG neurons from OVX and intac t animals, expression of both NGF receptor mRNAs was upregulated in se nsory neurons during proestrus, as compared to the OVX condition. Estr ogen replacement, on the other hand, resulted in a transient downregul ation of p75(NGFR) mRNA and a time-dependent upregulation of trkA mRNA . Estrogen regulation of NGF receptor mRNA in adult peripheral neural targets of the neurotrophins supports the hypothesis that estrogen may regulate neuronal sensitivity to neurotrophins such as NGF and may be an important mediator of neurotrophin actions in normal neural functi on and following neural trauma.