Role of pregnane xenobiotic receptor in the midbrain ventral tegmental area for estradiol- and 3α,5α-THP-facilitated lordosis of female rats.

Abstract

RATIONALE:

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.

OBJECTIVES:

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: C A Frye, C J Koonce, A A Walf
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 231 Issue 17 Pg. 3365-74 (Sep 2014) ISSN: 1432-2072 [Electronic] Germany
• PMID: 24435323 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Pregnane X Receptor
• Receptors, Steroid
• 20-alpha-Dihydroprogesterone
• Progesterone
• Estradiol
• Pregnanolone

Topics

• 20-alpha-Dihydroprogesterone (metabolism)
• Animals
• Anxiety (psychology)
• Estradiol (pharmacology)
• Female
• Interpersonal Relations
• Motor Activity (drug effects)
• Pregnane X Receptor
• Pregnanolone (pharmacology)
• Progesterone (metabolism)
• Rats
• Rats, Long-Evans
• Receptors, Steroid (drug effects)
• Sexual Behavior, Animal (drug effects)
• Ventral Tegmental Area (drug effects, metabolism)