title: Neurite outgrowth promoting effect of 17-β estradiol is mediated through estrogen receptor alpha in an olfactory epithelium culture.
abstract: Olfactory deficits are observed early in the course of chronic neurological disorders including Alzheimer's disease (AD). Estrogen treatment in post-menopausal women reduced the incidence of olfactory dysfunction, raising the possibility that estrogen treatment can cure olfactory deficits in preclinical stages of AD. In this study, we examined the estradiol׳s effects on neurite outgrowth in explant cultures of mouse olfactory epithelium (OE). We found that neurons in OE cultures treated with 100 pM 17-β estradiol (estradiol) had significantly longer neurite outgrowth than cultures treated with ethanol alone (vehicle). The OE neurons expressed estrogen receptors alpha (ERα) and ER beta (ERβ). Estrogen treatment upregulated both ERα and ERβ expression in OE culture. Treatment of OE cultures with propyl pyrazole triol (PPT), a selective agonist for ERα increased neurite outgrowth to comparable extent as estradiol treatment. In contrast, 2,3-bis-4-hydroxyphenyl (DPN), a specific agonist for ERβ, had no effect on neurite outgrowth. Furthermore, estradiol treatment increased neurite outgrowth in OE cultures derived from ERβ-deficient/knockout mice and wild-type littermates, but not in ERα-deficient/knockout mice. These data suggest that ERα mediates the neurite outgrowth promoting effects of estradiol in OE cultures. We propose that olfactory dysfunction in chronic neurological disorders, where estrogen deficiency is a risk factor, is an indicator of compromised axonal regeneration of olfactory sensory neurons.
authors.affiliation: Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston IL 61920, United States.
authors.forename: Apryl E
authors.initials: AE
authors.lastname: Pooley
authors.affiliation: Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston IL 61920, United States.
authors.forename: Minh
authors.initials: M
authors.lastname: Luong
authors.affiliation: Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston IL 61920, United States.
authors.forename: Aseem
authors.initials: A
authors.lastname: Hussain
authors.affiliation: Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston IL 61920, United States. Electronic address: bpnathan@eiu.edu.
authors.forename: Britto P
authors.initials: BP
authors.lastname: Nathan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D036145:Ginsenosides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009243:NAD / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009831:Olfactory Mucosa / Q000166:cytology*; D012502:Sapogenins / Q000494:pharmacology
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D036145:Ginsenosides; D012502:Sapogenins; C507965:ginsenoside 20S-protopanaxatriol; D009243:NAD; D004958:Estradiol
keywords: Estrogen; Estrogen receptors; Olfactory