title: Effects of estradiol valerate and remifemin on norepinephrine signaling in the brain of ovariectomized rats.
abstract: OBJECTIVE
  We investigated the norepinephrine pathway changes from the locus coeruleus (LC) to the preoptic area of the hypothalamus (POAH) in the brain of ovariectomized rats under low estrogen levels and explored the therapeutic effects of estradiol valerate (E2) and Remifemin (ICR) on these changes.
  
  
  METHODS
  40 female Sprague-Dawley rats were randomly divided into the following groups: surgery with vehicle (SHAM), ovariectomy surgery with vehicle (OVX), ovariectomy with E2 treatment (OVX + E2), and ovariectomy with Remifemin (OVX + ICR). After 4 weeks of treatment, we observed the changes by immunohistochemistry.
  
  
  RESULTS
  (1) The average optical density of DBH-ir fibers and the number of α1-adrenoreceptor- and estrogen receptor (ER)α-positive neurons in the main nuclei of POAH were all reduced in OVX rats compared with the SHAM group. The above changes were normalized in all nuclei of the POAH in the E2 group, while they were normalized in some nuclei in the ICR group. Coexpression of ERα and α1-adrenoreceptor was observed in the POAH. (2) The number of DBH- and ERα-positive neurons in the LC decreased in the OVX group compared with the SHAM group and increased after treatment with E2 and ICR. Coexpression of ERα and DBH was observed in the LC.
  
  
  CONCLUSIONS
  Low estrogen (OVX) altered norepinephrine synthesis in the LC, the projection of norepinephrine fibers and α1-adrenoreceptor expression in the POAH. Both E2 and ICR normalized the norepinephrine pathway, but E2 achieved greater effects than ICR. ICR had different effects in different nuclei in the POAH and its therapeutic effect was better in the LC.
authors.affiliation: Anatomy and Embryology Department, Peking University Health Science Center, Beijing, PR China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.forename: Wenpei
authors.initials: W
authors.lastname: Bai
authors.forename: Guangxia
authors.initials: G
authors.lastname: Cui
authors.forename: Biao
authors.initials: B
authors.lastname: Jin
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Jia
authors.forename: Yunmeng
authors.initials: Y
authors.lastname: Da
authors.forename: Lihua
authors.initials: L
authors.lastname: Qin
mesh_terms: D000818:Animals; D031885:Cimicifuga; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism*; D010052:Ovariectomy; D010936:Plant Extracts / Q000494:pharmacology*; D011301:Preoptic Area / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D010936:Plant Extracts; D018340:Receptors, Adrenergic, alpha-1; C073419:Remifemin; D004958:Estradiol; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine