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

Endocrinology. 2001 Jul;142(7):3261-4. doi: 10.1210/endo.142.7.8176.


Feedback regulation of luteinizing hormone-releasing hormone (LHRH) neurons by estradiol plays important roles in the neuroendocrine control of reproduction. Recently, we found that the majority of LHRH neurons in the rat contain estrogen receptor-beta (ER-beta) mRNA, whereas, they seemed to lack ER-alpha mRNA expression. In addition, we observed nuclear uptake of (125)I-estrogen by a subset of these cells. These data suggest that ER-beta is the chief 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 sections obtained from the preoptic area of rats. The improved ICC method using the silver-gold intensification of nickel-diaminobenzidine chromogen, enabled 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-primed female (74.9 +/- 3.2%) and intact male (85.0 +/- 4.7%) rats. The presence of ER-beta mRNA, ER-beta immunoreactivity and (125)I-estrogen binding sites in LHRH neurons of the rat provide strong support for the notion that these cells are directly regulated by estradiol, through ER-beta. The gene targets and molecular mechanisms of this regulation remain unknown.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / drug effects
  • Brain / metabolism*
  • Estradiol / pharmacology
  • Estrogen Receptor beta
  • Female
  • Gonadotropin-Releasing Hormone / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Neurons / metabolism*
  • Ovariectomy
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*


  • Estrogen Receptor beta
  • RNA, Messenger
  • Receptors, Estrogen
  • Gonadotropin-Releasing Hormone
  • Estradiol