Cytoplasmic estrogen receptors in rat brain: immunocytochemical evidence using three antibodies with distinct epitopes.

The existence of cytoplasmic estrogen receptors (ERs) has been reported in the guinea pig brain using immunocytochemical techniques. While cytoplasmic ERs have been reported recently in other species, such as opossum, musk shrew, and ferrets, an exclusively cell nuclear pattern of ER immunoreactivity has been reported in the rat brain. Because all studies that have reported the existence of cytoplasmic ERs in the brain have used the H 222 monoclonal antibody, the possibility exists that this observation is idiosyncratic to this antibody. In the present experiment three antibodies directed against diverse epitopes on the ER protein were used to immunocytochemically stain ERs in rat brain. With each antibody, ER immunoreactivity was observed in the hypothalamus, preoptic area, amygdala, and midbrain periaqueductal gray. In all cases we observed the highest density of reaction product in cell nuclei, but extensive cytoplasmic immunostaining was observed in most areas as well. In addition to demonstrating the existence of neural ER immunoreactivity in perikaryal cytoplasm and cytoplasmic processes in the brain, this study suggests that the neural cytoplasmic ER immunoreactivity is not just a small fragment of the receptor protein; rather, it is likely to be the entire receptor.