Research ReportNeurite outgrowth promoting effect of 17-β estradiol is mediated through estrogen receptor alpha in an olfactory epithelium culture

- Treatment of OE cultures with estradiol increased neurite outgrowth.
- The ERα agonist, but not ERβ agonist, increased neurite outgrowth in OE cultures.
- Estradiol increased neurite outgrowth in OE cultures from ERβ knockout mice.
- Estradiol had no effect on neurite outgrowth in OE cultures from ERα knockout mice.
- First evidence that estradiol, via ERα, promotes neurite outgrowth in OE cultures.

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.