Estrogen receptor-beta immunoreactivity in luteinizing hormone-releasing hormone neurons of the rat brain

Feedback regulation of luteinizing hormone-releasing hormone (LHRH) neurons by estradiol plays important roles in the neuroendocrine control of reprod uction. Recently, we found that the majority of LHRH neurons in the rat con tain estrogen reteptor-beta (ER-beta) mRNA. whereas, they seemed to lack ER alpha mRNA expression. In addition, we observed nuclear uptake of I-125-es trogen by a subset of these cells. These data suggest that ER-beta is the c hief receptor isoform mediating direct estrogen effects upon LHRH neurons. To verify the translation of ER-beta protein within LHRH cells, the present studies applied dual-label immunocytochemistry (ICC) to free-floating sect ions obtained from the preoptic area of rats. The improved ICC method using the silver-gold intensification of nickel-diaminobenzidine chromogen, enab led the observation of nuclear ER-beta -immunoreactivity in the majority of LHRH cells. The incidence of ER-beta expression was similarly high in LHRH neurons of ovariectomized female (87.8 +/-2.3%, mean +/- SEM). estradiol-p rimed female (74.9 +/-3.2%) and intact male (85.0 +/-4.7%) rats. The presen ce of ER-beta mRNA, ER-beta immunoreactivity and I-125-estrogen binding sit es in LHRH neurons of the rat provide strong support For the notion that th ese cells are directly regulated by estradiol, through ER-beta. The gene ta rgets and molecular mechanisms of this regulation remain unknown.