Sa. Scoville et al., ESTROGEN REGULATES NEUROFILAMENT GENE-EXPRESSION IN ADULT FEMALE RAT DORSAL-ROOT GANGLION NEURONS, Experimental neurology, 146(2), 1997, pp. 596-599
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.