ESTROGEN REGULATES NEUROFILAMENT GENE-EXPRESSION IN ADULT FEMALE RAT DORSAL-ROOT GANGLION NEURONS

Recently, adult female dorsal root ganglion (DRG) neurons were shown t o express the estrogen receptor gene and to bind estrogen, This gene e xpression and binding is hormone dependent. Moreover, in a subpopulati on of DRG neurons, the estrogen receptor is colocalized with high-affi nity (trkA) and low-affinity (p75(NGFR)) receptors for nerve growth fa ctor (NGF). In this NGF-responsive subpopulation of DRG neurons, estro gen regulates expression of the NGF receptor genes and may increase th e sensitivity of these cells to the neurotrophin. The present study te sted the hypothesis that neurofilament gene expression, which is regul ated by NGF in these cells, is dependent on hormone status, In this st udy, ovariectomized (OVX) rats received either long-term physiological estrogen (conjugated estrogens; Premarin, Wyeth-Ayerst) replacement ( low dose) or 10 times physiological levels (high dose). Quantitative i n situ hybridization with an RNA probe for the 68-kDa neurofilament mR NA revealed a significant dose-dependent effect of Premarin on DRG neu rofilament gene expression, In OVX animals receiving low-dose Premarin replacement therapy the mean steady-state 68-kDa mRNA level was as hi gh as 4 times that of untreated OVX rats. High-dose therapy increased the mean 68-kDa neurofilament steady-state mRNA level to as much as si x-fold that observed in untreated OVX animals. The estrogen-dependent upregulation of neurofilament gene expression appeared to occur in all DRG neurons,rather than in a subpopulation of those cells. These data suggest an important role for estrogen in the maintenance and functio n of primary sensory neurons. Whether estrogen directly regulates neur ofilament gene expression or indirectly regulates it by increasing DRG neuronal sensitivity to neurotrophins or other growth factors remains to be determined. (C) 1997 Academic Press.