Detection of estrogen receptor-beta messenger ribonucleic acid and 125I-estrogen binding sites in luteinizing hormone-releasing hormone neurons of the rat brain

Endocrinology. 2000 Sep;141(9):3506-9. doi: 10.1210/endo.141.9.7788.


Luteinizing hormone-releasing hormone (LHRH) neurons of the forebrain play a pivotal role in the neuroendocrine control of reproduction. Although serum estrogen levels influence many aspects of LHRH neuronal activity in the female, earlier studies were unable to detect estrogen receptors (ERs) within LHRH neurons, thus shaping a consensus view that the effects of estradiol on the LHRH neuronal system are mediated by interneurons and/or the glial matrix. The present studies used dual-label in situ hybridization histochemistry (ISHH) and combined LHRH-immunocytochemistry/125I-estrogen binding to readdress the estrogen-receptivity of LHRH neurons in the female rat. In ISHH experiments we found that the majority of LHRH neurons exhibited hybridization signal for the "beta" form of ER (ER-beta). The degree of colocalization was similar in topographically distinct populations of LHRH neurons and was not significantly altered by estradiol (67.2+/-1.8% in ovariectomized and 73.8+/-4.2% in ovariectomized and estradiol-treated rats). In contrast, the mRNA encoding the classical ER-alpha could not be detected within LHRH neurons. In addition, in vivo binding studies using 125I-estrogen revealed a subset of LHRH-immunoreactive neurons (8.8%) which accumulated the radioligand thus providing evidence for the translation of ER protein(s) within these cells. The findings that most LHRH neurons in the female rat express ER-beta mRNA and at least some are capable of binding 125I-estrogen challenge the current opinion that estrogen does not exert direct effects upon the LHRH neuronal system.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Brain / cytology
  • Brain Chemistry / physiology*
  • Estrogen Receptor beta
  • Female
  • Gonadotropin-Releasing Hormone / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Neurons / metabolism*
  • Ovariectomy
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Estrogen / biosynthesis*
  • Receptors, Estrogen / genetics


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