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Endocrinology Vol. 144, No. 5 2055-2067
Copyright © 2003 by The Endocrine Society

Immunolocalization of Estrogen Receptor ß in the Mouse Brain: Comparison with Estrogen Receptor {alpha}

Sudha Warrier Mitra, Elena Hoskin, Joel Yudkovitz, Lisset Pear, Hilary A. Wilkinson, Shinji Hayashi, Donald W. Pfaff, Sonoko Ogawa, Susan P. Rohrer, James M. Schaeffer, Bruce S. McEwen and Stephen E. Alves

Department of Atherosclerosis and Endocrinology, Merck Research Laboratories (S.W.M., J.Y., L.P., H.A.W., S.P.R., J.M.S., S.E.A.), Rahway, New Jersey 07065; Laboratory of Endocrinology, Graduate School of Integrated Science, Yokohama City University (S.H.), Yokahama 236-0027, Japan; and Departments of Neuroendocrinology (E.H., B.S.M.) and Neurobiology and Behavior (D.W.P., S.O.), Rockefeller University, New York, New York 10021

Address all correspondence and requests for reprints to: Stephen E. Alves, Ph.D., Department of Atherosclerosis and Endocrinology, Merck Research Laboratories, 126 Lincoln Avenue (RY 80T-126), Rahway, New Jersey 07065. E-mail: stephen_alves{at}merck.com.

Estrogen receptor {alpha} (ER{alpha}) and ERß are members of the steroid nuclear receptor family that modulate gene transcription in an estrogen-dependent manner. ER mRNA and protein have been detected both peripherally and in the central nervous system, with most data having come from the rat. Here we report the development of an ERß-selective antibody that cross-reacts with mouse, rat, and human ERß protein and its use to determine the distribution of ERß in the murine brain. Further, a previously characterized polyclonal antibody to ER{alpha} was used to compare the distribution of the two receptors in the first comprehensive description of ER distribution specifically in the mouse brain. ERß immunoreactivity (ir) was primarily localized to cell nuclei within select regions of the brain, including the olfactory bulb, cerebral cortex, septum, preoptic area, bed nucleus of the stria terminalis, amygdala, paraventricular hypothalamic nucleus, thalamus, ventral tegmental area, substantia nigra, dorsal raphe, locus coeruleus, and cerebellum. Extranuclear-ir was detected in several areas, including fibers of the olfactory bulb, CA3 stratum lucidum, and CA1 stratum radiatum of the hippocampus and cerebellum. Although both receptors were generally expressed in a similar distribution through the brain, nuclear ER{alpha}-ir was the predominant subtype in the hippocampus, preoptic area, and most of the hypothalamus, whereas it was sparse or absent from the cerebral cortex and cerebellum. Collectively, these findings demonstrate the region-selective expression of ERß and ER{alpha} in the adult ovariectomized mouse brain. These data provide an anatomical framework for understanding the mechanisms by which estrogen regulates specific neural systems in the mouse.




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