Progesterone-facilitated lordosis of estradiol-primed mice is attenuated by knocking down expression of membrane progestin receptors in the midbrain

Cheryl A Frye; Alicia A Walf; Amy S Kohtz; Yong Zhu

doi:10.1016/j.steroids.2013.11.009

Progesterone-facilitated lordosis of estradiol-primed mice is attenuated by knocking down expression of membrane progestin receptors in the midbrain

Steroids. 2014 Mar:81:17-25. doi: 10.1016/j.steroids.2013.11.009. Epub 2013 Nov 20.

Authors

Cheryl A Frye¹, Alicia A Walf², Amy S Kohtz³, Yong Zhu⁴

Affiliations

¹ Dept. of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA; Dept. of Biological Sciences, The University at Albany-SUNY, Albany, NY 12222, USA; The Center for Neuroscience, The University at Albany-SUNY, Albany, NY 12222, USA; The Center for Life Science Research, The University at Albany-SUNY, Albany, NY 12222, USA; Dept. of Chemistry, The University of Alaska-Fairbanks, IDeA Network of Biomedical Excellence (INBRE), Fairbanks, AK 99775, USA. Electronic address: cafrye@alaska.edu.
² Dept. of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA; Dept. of Chemistry, The University of Alaska-Fairbanks, IDeA Network of Biomedical Excellence (INBRE), Fairbanks, AK 99775, USA; Cognitive Science Department, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA.
³ Dept. of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA.
⁴ Dept. of Biology, East Carolina University, Greenville, NC 27858-4353, USA.

Abstract

Evidence is emerging of the role of membrane progestin receptors (referred to as mPRs herein: members of Progestin and AdipoQ Receptor (Paqr) family) as a novel brain target in mammals, such as rats. In the present study, the role of mPRs in mice was assessed to further elucidate the conservation of this mechanism across species. The brain target investigated was the midbrain ventral tegmental area (VTA) given its described role for rapid actions of progestins for reproduction. Studies tested the hypothesis that if mPRs are required for progestin-facilitated lordosis through actions in the VTA, then knockdown of mPRs in the VTA will attenuate lordosis. Ovariectomized (OVX) mice were subcutaneously injected with estradiol (E2) and progesterone (P4), and infused with antisense oligodeoxynucleotides (AS-ODNs) to mPRα (Paqr7) and/or mPRβ (Paqr8) or vehicle to the lateral ventricle or VTA. Mice were assessed for reproductive behavior (lordosis and aggression/rejection quotients) in a standard mating task. Results supported our hypothesis. E2+P4-facilitated lordosis was significantly reduced, and aggression/rejection increased, with infusions of mPRα, mPRβ, or mPRαβ AS-ODNs to the lateral ventricle, compared to vehicle. E2+P4-facilitated lordosis was significantly decreased, and aggression/rejection increased, with mPRβ or mPRαβ AS-ODNs to the VTA of C57/BL6 mice. Both mPRɑ and mPRβ AS-ODNs reduced lordosis, and increased aggression/rejection, of wildtype (C57/BL6x129) mice, but not nuclear PR knockout mice. Thus, mPRs may be a novel target of progestins for reproductive behavior of mice.

Keywords: Neurosteroids; Nongenomic; Progestin; Reproduction.

Publication types

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

MeSH terms

Aggression / drug effects
Aggression / physiology
Animals
Estradiol / metabolism*
Estradiol / pharmacology
Female
Male
Membrane Proteins / genetics
Mesencephalon / physiology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovariectomy
Posture
Progesterone / pharmacology*
Receptors, Progesterone / genetics*
Receptors, Progesterone / metabolism*
Sexual Behavior, Animal / drug effects*

Substances

Membrane Proteins
PGLP protein, mouse
Paqr8 protein, mouse
Receptors, Progesterone
progesterone receptor A
progesterone receptor B
Progesterone
Estradiol

Grants and funding

R15 GM100461/GM/NIGMS NIH HHS/United States