DOPAMINERGIC PHENOTYPE INDUCED BY ESTROGENS IN A HUMAN NEUROBLASTOMA CELL-LINE

Oestrogens are the key factor in the sexual differentiation of the mam malian brain and play an important role in the activity of selected ar eas of the mature brain. To pursue the study of oestrogen action on ne ural cells at the molecular level, we developed a human neuroblastoma cell line (SK-ER3) expressing the oestrogen receptor (ER). Treatment o f these cells with 17 beta-oestradiol causes growth arrest and morphol ogical and biochemical differentiation. The aim of the present study w as to investigate whether oestrogen-differentiated SK-ER3 neuroblastom a cells acquire the ability to synthesize a specific neurotransmitter and whether the growth arrest previously reported can be ascribed to t he blockage of the cells at a specific stage of the cell cycle. The re sults presented here indicate that oestrogens induce accumulation of S K-ER3 cells in the GO phase of the cell cycle, underscoring the acquis ition of a mature neural phenotype upon hormonal treatment. Most impor tantly, we show that in the differentiated cells the content of tyrosi ne hydroxylase and Na+-dependent dopamine uptake is significantly augm ented, proving that the oestrogen-differentiated SK-ER3 cells can synt hesize and store a specific neurotransmitter. In addition, we prove th at the dopamine accumulated in differentiated SK-ER3 cells can be rele ased. These studies therefore suggest that oestrogen treatment results in the acquisition of a fully functional dopaminergic phenotype of SK -ER3 cells. Ample evidence shows a link between dopaminergic neurons a nd oestrogen activity in hypothalamic and non-hypothalamic areas of th e mammalian brain. Our study indicates that oestrogens might play a pr imary role in committing undifferentiated neuroblasts towards the dopa minergic phenotype.