Effects of Short-Term Estrogen Replacement on trkA mRNA Levels in Axotomized Dorsal Root Ganglion Neurons

• Published in: Experimental neurology 1999-10, Vol.159 (2), p.433-440
• Main Authors: Liuzzi, Francis J., Scoville, Sheila A., Bufton, Susan M.
• Format: Article
• Language: English
• Subjects: Animals; Axotomy; Biological and medical sciences; Drug Implants; Estradiol - administration & dosage; Estradiol - pharmacology; estrogen receptor; Estrogen Replacement Therapy; Female; Ganglia, Spinal - cytology; Ganglia, Spinal - physiology; Gene Expression Regulation; growth factors; Hormones. Endocrine system; Medical sciences; Nerve Growth Factors - physiology; Neurons - cytology; Neurons - drug effects; Neurons - physiology; NGF; Ovariectomy; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Receptor, trkA - genetics; RNA, Messenger - genetics; Sciatic Nerve - physiology; sciatic nerve transection; Transcription, Genetic - drug effects
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.1999.7169

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 expression and function. Recently, a number of laboratories reported the presence of estrogen receptors in DRG neurons and profound effects of estrogen on DRG gene expression. Our laboratory, for example, has reported a significant and coordinate decrease in DRG trkA and β-preprotachykinin (β-PPT) mRNA levels following 90 days of daily estrogen injections to ovariectomized (OVX) rats. These data suggest, as has been suggested for medial septal cholinergic neurons, that estrogen may collaborate with NGF in the regulation of DRG neuronal gene expression and function. The current study examined further this potential collaboration in the DRG by determining the effect of short-term estrogen replacement in OVX rats on DRG trkA mRNA levels following sciatic nerve transection and the resulting removal of a vital source of NGF for those cells. In OVX rats, about 40% of lumbar DRG neurons contained trkA mRNA. Short-term estrogen replacement had no effect on the percentage 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, partially and significantly restored the mean trkA mRNA level. It was 49% greater than that of the untreated axotomized DRGs. It did not, however, significantly increase the percentage of DRG neurons containing trkA in axotomized 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 estrogen demonstrated in our previous study. Moreover, the current data show that estrogen regulates trkA mRNA levels in the absence of target-derived NGF. These data suggest that estrogen may collaborate with NGF in the maintenance 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 of ongoing neuropathic processes.