Abstract
Effects of N-methyl-D-aspartate (NMDA) receptor (NMDAR) activation on neuroendocrine function can be modulated by the steroid hormone milieu. For example, the hypothalamic GnRH neurons, the primary cells regulating reproductive function, are stimulated by NMDAR agonists, and this is greatly potentiated by estrogen. We hypothesized that the actions of glutamate and estrogen may converge at target cells in the brain in which the NMDA and estrogen receptors (ERs) are coexpressed. To this end, we used quantitative stereological techniques to determine the colocalization of the obligatory NMDAR subunit, NR1, and the ERα, in the anteroventral periventricular nucleus and the medial preoptic nucleus, two critical regions for reproductive physiology and behavior. We observed extensive colocalization of ERα and NR1 in these brain regions (∼80%). In the anteroventral periventricular nucleus, treatment of ovariectomized rats with estrogen up-regulated the coexpression, whereas in the medial preoptic nucleus, estrogen had no effect, demonstrating a regional specificity to the estrogen sensitivity. The number of ERα cells that did not express NR1 was not altered by estrogen treatment in either brain region. Thus, we speculate that the extensive colocalization of ERα and the NMDAR provides an anatomical level at which estrogen and glutamate can act at target cells, and potentially synergize, to influence neuroendocrine and autonomic functions.