Dopaminergic activation of estrogen receptors in developing brain

Steroid hormone receptor activation regulates many physiological and behavior processes in a variety of species, including humans. In many vertebrates, steroid receptor activity within the developing brain plays a major role in sexually differentiating brain and behavior. Although it was previously believed that steroid receptors could be activated only by binding to a cognate ligand, recent evidence indicates that steroid receptors can also be activated in the absence of steroid hormones, a process called ligand-independent activation. One factor known to activate estrogen receptors in a ligand-independent manner in vitro is the neurotransmitter dopamine. Because dopamine is highly responsive to environmental stimuli, the existence of such a pathway within the developing brain could provide a mechanism for the environment to alter sexual differentiation. Here I present evidence that dopamine can act in an estrogen receptor-mediated manner to alter neuronal activity and gene expression within restricted regions of the developing rat brain, as well as influence the development of sexually dimorphic juvenile social play behavior. I also demonstrate that a prominent environmental stimulus, maternal grooming, can alter activity of the dopaminergic system, suggesting that environmental factors may act via dopamine to alter estrogen receptor activity. These data contribute to the growing body of evidence that factors other than steroid hormones may play important roles in sexual differentiation.