title: Role of pregnane xenobiotic receptor in the midbrain ventral tegmental area for estradiol- and 3α,5α-THP-facilitated lordosis of female rats.
abstract: BACKGROUND
  Progesterone and its metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), have actions in the ventral tegmental area (VTA) that are required for lordosis, a characteristic mating posture of female rodents. 17β-estradiol (estradiol) co-varies with progestogens over natural cycles, enhances production of 3α,5α-THP, and is required for successful reproductive behavior.
  
  
  OBJECTIVE
  A question of interest is the role of pregnane xenobiotic receptor (PXR), a nuclear receptor that regulates enzymes needed for the production of 3α,5α-THP, for estradiol-mediated lordosis. The hypothesis tested was that if PXR is involved in estradiol-mediated biosynthesis of 3α,5α-THP and reproductive behavior, knocking down expression of PXR in the VTA of estradiol-primed, but not vehicle-primed, rats should decrease lordosis and midbrain 3α,5α-THP; effects may be attenuated by 3α,5α-THP administered to the VTA.
  
  
  METHODS
  Ovariectomized rats were administered subcutaneous injections of oil vehicle or estradiol. Rats were then administered PXR antisense oligonucleotides (PXR AS-ODNs; which are expected to locally knock down expression of PXR), or control (saline), infusions to the VTA. Rats were administered 3α,5α-THP or vehicle via infusions to the VTA. Reproductive behavior (paced mating task) of rats was determined in addition to exploratory (open field), affective (elevated plus maze), and pro-social (social interaction task) behavior.
  
  
  RESULTS
  Reproductive behavior (i.e., increased lordosis) was enhanced with estradiol-priming and infusions of 3α,5α-THP to the VTA. Infusions of PXR AS-ODNs to the VTA attenuated responses in estradiol-, but not vehicle-, primed rats, compared to control infusions.
  
  
  CONCLUSIONS
  PXR may be involved in a neuroregulatory response involving biosynthesis of 3α,5α-THP in the midbrain VTA of estradiol-primed rats.
authors.affiliation: Department of Psychology, The University at Albany-SUNY, Life Sciences 01058, 1400 Washington Ave., Albany, NY, 12222, USA, cheryl.a.frye@gmail.com.
authors.forename: C A
authors.initials: CA
authors.lastname: Frye
authors.forename: C J
authors.initials: CJ
authors.lastname: Koonce
authors.forename: A A
authors.initials: AA
authors.lastname: Walf
mesh_terms: D004092:20-alpha-Dihydroprogesterone / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000523:psychology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007398:Interpersonal Relations; D009043:Motor Activity / Q000187:drug effects; D000077297:Pregnane X Receptor; D011280:Pregnanolone / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011987:Receptors, Steroid / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D004092:20-alpha-Dihydroprogesterone; D011374:Progesterone; D004958:Estradiol; D011280:Pregnanolone