Estradiol increases Pet-1 and serotonin transporter mRNA in the midbrain raphe nuclei of ovariectomized rats

Brain Res. 2009 Mar 9:1259:51-8. doi: 10.1016/j.brainres.2008.12.067. Epub 2009 Jan 10.


Previous research has shown that estradiol increases the anorexia associated with serotonin (5-HT) neurotransmission. To examine further the putative relationship between estradiol and 5-HT, we investigated whether estradiol increases the expression of Pet-1 and the 5-HT transporter (5-HTT), two genes implicated in the development and regulation of the 5-HT system. Ovariectomized (OVX) rats (n=5-6/group) were treated with 0, 2, or 10 microg estradiol benzoate (EB) in sesame oil on 2 consecutive days. Food intake and body weight were recorded 2 days later when EB-treated rats typically display signs of behavioral estrus (e.g., reduced feeding). Following the collection of behavioral data, rats were perfused, brains were removed, and coronal sections were cut through the midbrain raphe nuclei. Pet-1 and 5-HTT mRNA levels were quantified throughout the dorsal and median raphe nuclei (DRN and MRN) by conducting in situ hybridization on free-floating tissue sections using (35)S-labeled cDNA probes. As expected, EB treatment decreased food intake and body weight on the day that modeled estrus. At this same time, EB treatment increased Pet-1 and 5-HTT mRNA levels within the DRN and MRN. We conclude that a physiologically relevant regimen of estradiol treatment in OVX rats increases Pet-1 and 5-HTT mRNA levels in the midbrain raphe nuclei at a time when the anorexigenic effect of estradiol is apparent. Further studies are required to determine whether the increased expression of Pet-1 and 5-HTT mRNA plays a causal role in the anorexigenic effect of estradiol.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Appetite Depressants / administration & dosage
  • Appetite Depressants / pharmacology
  • Body Weight
  • Eating / drug effects
  • Estradiol / administration & dosage
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology
  • Estrus / drug effects
  • Female
  • Gene Expression / drug effects
  • In Situ Hybridization
  • Ovariectomy*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / metabolism*
  • Rats
  • Rats, Long-Evans
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Appetite Depressants
  • Fev protein, rat
  • RNA, Messenger
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, rat
  • Transcription Factors
  • estradiol 3-benzoate
  • Estradiol