Biologically active estrogen receptor-beta: Evidence from in vivo autoradiographic studies with estrogen receptor alpha-knockout mice

Estrogen receptor-beta (ERP) 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 I-125-estrogen, a compound with a similar affinity for both ERs to ascertai n whether ER beta mRNA is translated into biologically active receptor. Mic e were injected with I-125-estrogen, and sections were mounted on slides an d opposed to emulsion. After exposure,labeled cells were seen in ER alpha K O brain regions where ER beta is expressed (preoptic and paraventricular nu clei of the hypothalamus; bed nucleus of the stria terminalis; amygdala; en torhinal cortex; and dorsal raphe). Competition studies with 17 beta-estrad iol eliminated binding in the ER alpha KO brain, whereas 16 alpha IE2, an E R alpha selective agonist and dihydrotestosterone had no effect. In contras t, competition studies with 16 alpha IE2 in wild-type mice eliminated I-125 - estrogen binding to ER alpha and resulted in a pattern of residual bindin g 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 alph a KO brain where ER beta is expressed, brain regions that were also seen af ter eliminating binding to ER alpha in wild-type mice. These data provide t he first evidence that ER beta mRNA is translated into a biologically activ e protein in the rodent brain.