Effects of short-term estrogen replacement on trkA mRNA levels in axotomized dorsal root ganglion neurons

A population of adult dorsal root ganglion (DRG) neurons bind NGF with high affinity and express the trkA gene. In these cells, NGF regulates gene exp ression and function. Recently, a number of laboratories reported the prese nce of estrogen receptors in DRG neurons and profound effects of estrogen o n DRG gene expression. Our laboratory, for example, has reported a signific ant and coordinate decrease in DRG trkA and beta-preprotachykinin (P-PPT) m RNA levels following 90 days of daily estrogen injections to ovariectomized (OVX) rats. These data suggest, as has been suggested for medial septal ch olinergic neurons, that estrogen may collaborate with NGF in the regulation of DRG neuronal gene expression and function. The current study examined f urther this potential collaboration in the DRG by determining the effect of short-term estrogen replacement in OVX rats on DRG trkA mRNA levels follow ing sciatic nerve transection and the resulting removal of a vital source o f NGF for those cells. In OVX rats, about 40% of lumbar DRG neurons contain ed trkA mRNA, Short-term estrogen replacement had no effect on the percenta ge of neurons containing trkA mRNA, but increased the mean trkA mRNA level in uninjured DRGs of OVX rats by 23%, Axotomy in OVX rats reduced the mean trkA mRNA level by 55% but did not significantly decrease the percentage of neurons containing the mRNA. Estrogen replacement, 7 days after axotomy, p artially and significantly restored the mean trkA mRNA level. It was 49% gr eater than that of the untreated axotomized DRGs. It did not, however, sign ificantly increase the percentage of DRG neurons containing trkA in axotomi zed DRGs. These observations show that short-term estrogen has an opposite effect on DRG neuronal trkA mRNA levels as compared to that of long-term es trogen demonstrated in our previous study. Moreover, the current data show that estrogen regulates trkA mRNA levels in the absence of target-derived N GF. These data suggest that estrogen may collaborate with NGF in the mainte nance of normal adult DRG gene expression and function. Furthermore, these data suggest that loss of estrogen, such as that associated with menopause, may contribute to a decline in DRG neuronal function and an exacerbation o f ongoing neuropathic processes. (C) 1999 Academic Press.