Estrogen alters trkA and p75 neurotrophin receptor expression within sympathetic neurons

Survival and growth of sympathetic neurons is regulated by nerve growth factor acting through trkA and p75^NTR receptors. Sympathetic neurons are also affected by gonadal steroid hormones, particularly estrogen. To determine if estrogen may influence sympathetic neurons via altered neurotrophin receptor expression, we investigated effects of acute or chronic estrogen administration on levels of trkA and p75^NTR proteins, numbers of immunoreactive neurons, and numbers of neurons expressing trkA, p75 ^NTR, and estrogen receptor-α transcripts. Superior cervical ganglia from ovariectomized or estradiol-treated rats were processed for in situ hybridization or immunohistochemistry, and percentages of stained neurons quantitated or processed for Western blot analysis. In ovariectomized rats, approximately 50% of sympathetic neurons expressed trkA mRNA and protein. Acute estrogen administration did not affect trkA transcript expression, but reduced trkA protein significantly. Chronic treatment did not alter neuronal trkA expression. Approximately 70% of sympathetic neurons in ovariectomized rats expressed p75^NTR transcripts and about 50% showed p75^NTR immunoreactivity. Acute estrogen did not affect p75^NTR expression. However, chronic estrogen reduced p75^NTR mRNA and protein expression significantly. Fifty to sixty percent of sympathetic neurons in ovariectomized rats displayed estrogen receptor-α mRNA. After acute estrogen administration, estrogen receptor-α transcript expression increased by 35%, although this was not maintained chronically. These findings indicate that estrogen can influence sympathetic neuronal neurotrophin receptor expression as well as estrogen receptor-α. Reduced trkA expression after acute estrogen may transiently predispose neurons to degenerative events, while diminished p75^NTR expression by chronic estrogen administration may exert long-term effects on survival or axonal outgrowth in sympathetic neurons.