Expression of Functional Estrogen Receptor β in Locus Coeruleus-Derived Cath.a Cells

Estrogen may have an important role in the brain beyond the development and regulation of reproductive function. Gender differences in the incidence of depression suggest that regulation of mood represents one such action. The locus coeruleus, a brain stem noradrenergic nucleus implicated in mood regulation, concentrates [(3)H]estradiol, but expression of the two estrogen receptor (ER) subtypes (ERalpha and ERbeta) varies across species. Further, the role of each subtype in estrogen action on noradrenergic neurons is unknown. We examined the expression of ERs in the Cath.a (central-adrenergic-tyrosine-hydroxylase-expressing) cell line derived from mouse brain stem and found that they express ERbeta protein but not ERalpha protein. Transient transfection assays using an estrogen-responsive reporter gene indicate that ERbeta is functional. The pure estrogen antagonist ICI 182,780 completely abolished estrogen's effects. Selective ER modulator results suggest that ER in Cath.a cells behaves in a manner consistent with ERbeta pharmacology. R,R-Tetrahydrochrysene, an ERalpha agonist, had no effect on luciferase-driven activity in Cath.a cells. This study provides the first report of a cell line that spontaneously expresses functional ERbeta protein. Cath.a cells may prove to be a useful tool in elucidating basic pharmacologic properties of ERbeta. It may also help reveal the molecular mechanisms involved in mood regulation by estrogen.