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 [³H]-estradiol, but expression of the two estrogen receptor (ER) subtypes (ER and ER) 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 cell line derived from mouse brain stem and found that they express ER protein, but not ER protein. Transient transfection assays using an estrogen-responsive reporter gene indicate that ER is functional. The pure estrogen antagonist ICI 182,780 completely abolished estrogen's effects. Selective estrogen receptor modulator (SERM) results suggest that estrogen receptor in Cath.a cells behaves in a manner consistent with ER pharmacology. R,R-THC, an ER 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 ER protein. Cath.a cells may prove useful tool in elucidating basic pharmacologic properties of ER. It may also help reveal the molecular mechanisms involved in mood regulation by estrogen.