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 p75NTR 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 p75NTR proteins, numbers of immunoreactive neurons, and numbers of neurons expressing trkA, p75NTR, and estrogen receptor-alpha 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 p75NTR transcripts and about 50% showed p75NTR immunoreactivity. Acute estrogen did not affect p75NTR expression. However, chronic estrogen reduced p75NTR mRNA and protein expression significantly. Fifty to sixty percent of sympathetic neurons in ovariectomized rats displayed estrogen receptor-alpha mRNA. After acute estrogen administration, estrogen receptor-alpha 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-alpha. Reduced trkA expression after acute estrogen may transiently predispose neurons to degenerative events, while diminished p75NTR expression by chronic estrogen administration may exert long-term effects on survival or axonal outgrowth in sympathetic neurons.
Hasan
Wohaib
W
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Mail Stop 3051, Kansas City, Kansas 66160, USA. whasan@kumc.edu
Smith
H Jesse
HJ
Ting
Alison Y
AY
Smith
Peter G
PG
D000818:Animals; D015153:Blotting, Western; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*
D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D004958:Estradiol; D020917:Receptor, trkA