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Endocrinology Vol. 140, No. 6 2613-2620
Copyright © 1999 by The Endocrine Society

ARTICLES

Biologically Active Estrogen Receptor-ß: Evidence from in Vivo Autoradiographic Studies with Estrogen Receptor {alpha}-Knockout Mice

Paul J. Shughrue, Malcolm V. Lane and Istvan Merchenthaler

Women’s Health Research Institute, Wyeth-Ayerst Research, Radnor, Pennsylvania 19087

Address all correspondence and requests for reprints to: Dr. Paul J. Shughrue, Women’s Health Research Institute, Wyeth-Ayerst Research, 145 King of Prussia Road, Radnor, Pennsylvania 19087. E-mail: shughrp{at}war.wyeth.com

Estrogen receptor-ß (ERß) messenger RNA (mRNA) has been detected in the brain of wild-type and estrogen receptor-{alpha} knockout (ER{alpha}KO) mice. The present study used in vivo autoradiography to evaluate the binding of 125I-estrogen, a compound with a similar affinity for both ERs to ascertain whether ERß mRNA is translated into biologically active receptor. Mice were injected with 125I-estrogen, and sections were mounted on slides and opposed to emulsion. After exposure, labeled cells were seen in ER{alpha}KO brain regions where ERß is expressed (preoptic and paraventricular nuclei of the hypothalamus; bed nucleus of the stria terminalis; amygdala; entorhinal cortex; and dorsal raphe). Competition studies with 17ß-estradiol eliminated binding in the ER{alpha}KO brain, whereas 16{alpha}IE2, an ER{alpha} selective agonist and dihydrotestosterone had no effect. In contrast, competition studies with 16{alpha}IE2 in wild-type mice eliminated 125I-estrogen binding to ER{alpha} and resulted in a pattern of residual binding comparable to that seen in the ER{alpha}KO brain. The results demonstrate that residual estrogen binding sites are present in regions of the ER{alpha}KO brain where ERß is expressed, brain regions that were also seen after eliminating binding to ER{alpha} in wild-type mice. These data provide the first evidence that ERß mRNA is translated into a biologically active protein in the rodent brain.




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