Classical and nonclassical estrogen action in the developing midbrain.

There is widespread acceptance that estrogen is involved in various steps of cellular differentiation during brain development. In the past years, we have demonstrated such a developmental role for estrogen in the rodent midbrain. Precisely, estrogen affects midbrain dopamine neurons with respect to functional and morphological maturation. On the cellular level, estrogen may act classically by binding and activating its respective nuclear receptors, thereby controlling the transcription of target genes. On the other hand, many estrogen effects in the CNS are transmitted nonclassically by interactions with putative membrane receptors and by stimulating distinct intracellular signaling cascades. In the midbrain, classical and nonclassical estrogen signaling routes operate side by side to ensure the proper development of dopaminergic cells. In the present report, we detail some of the cellular and molecular events which are activated by estrogen and are thought to take part in the estrogen-mediated stimulation of dopamine neuron differentiation.